Assessment of AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in patients with colorectal cancer: A stage-wise analysis

Assessment of AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in patients with colorectal cancer: A stage-wise analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessment of AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in patients with colorectal cancer: A stage-wise analysis Bahareh Shateri Amiri, Mohammad Sadegh Bazgoshaeyan, Younes Robati, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7426295/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background: Colorectal cancer (CRC) is the third most common malignancy globally and a leading cause of cancer-related death. Liver dysfunction and metastasis remain major contributors to poor outcomes. Noninvasive biomarkers such as the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) and the Albumin-Bilirubin (ALBI) score have shown potential in assessing liver function and predicting prognosis, but their stage-wise relevance in CRC is not well established. Methods: This retrospective observational study included 212 CRC patients aged ≥ 40 years admitted to Rasoul-e-Akram and Sina hospitals between 2015 and 2025. Patients were categorized into primary (stages 1 and 2) and advanced (stages 3 and 4) groups. APRI and ALBI scores were calculated from blood parameters and compared across stages using one-way ANOVA, chi-square, and Fisher’s exact tests. Odds ratios (OR) with 95% confidence intervals (CI) were computed, with p -value < 0.05 considered statistically significant. Results: Of the included patients, 57% had primary-stage CRC and 43% advanced-stage CRC. Both APRI and ALBI scores increased significantly with advancing cancer stage. Compared with primary stages, APRI showed an OR of 3.725 (95% CI: 1.723–7.783) and ALBI an OR of 1.926 (95% CI: 1.006–3.591) for advanced disease. Stage-wise analysis revealed that APRI ( p -value = 0.0128) and ALBI ( p -value = 0.03) were significantly higher in stage 4 compared to stage 3, with similar differences observed against earlier stages. Conclusion: APRI and ALBI scores increase with CRC progression, with the most pronounced elevations in stage 4. These indices offer simple, noninvasive, and cost-effective tools for assessing disease severity and guiding clinical decision-making. Prospective multicenter studies are needed to validate their prognostic utility and to establish standardized cut-off values. Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction 1.1 Background on CRC Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide and is the second leading cause of cancer-related mortality, resulting in approximately 600,000 deaths each year (1, 2). It is estimated that CRC cases will increase to 3.2 million, with mortality rising to 1.6 million by 2040 (3). There remains an urgent need for further investigation into noninvasive biomarkers for early diagnosis, as well as the discovery of innovative therapeutic targets for CRC (4). 1.2 Hepatic dysfunction and metastasis in CRC and its evaluation Some of the most challenging complications of colorectal cancer (CRC) are hepatic dysfunction and metastasis, which create difficulties in treating this prevalent malignancy. Liver metastasis is common in nearly 20-50% of CRC cases, is significantly associated with disease-related mortality (5, 6). Due to vast vascular connection with the gastrointestinal tract, the liver is the most common site of distant metastasis with tumors spreading through the portal vein (7, 8). Furthermore, chronic inflammation, such as non-alcoholic fatty liver disease (NAFLD), has been shown to elevate the risk of liver metastasis (9). Predicting liver metastases by evaluating systemic inflammatory markers has received attention, especially systemic immune-inflammatory index (10). Moreover, novel biomarkers, including specific microRNAs, show potential in evaluating metastasis risk and therapeutic response (11). 1.3 Introduction to ALBI and APRI score The albumin-bilirubin (ALBI) score is a clinical scoring system, including two routine blood test parameters: serum albumin and total bilirubin levels, which is used to evaluate the liver function, especially in patients with hepatocellular carcinoma (HCC) and other liver-related conditions (12-14). It should be noted that research has shown a significant correlation between ALBI score and prognostic outcomes in various cancers, including colorectal cancer (CRC). It has been shown that higher baseline scores indicate poorer overall survival (OS) and progression-free survival (PFS) (14-16). Additionally, the preoperative ALBI score has been established as a substantial predictor of immediate outcomes following radical surgery (15, 16). Studies have shown ALBI score can be used in patients with liver metastases to assess function of the liver and overall prognosis (15). The Aspartate Aminotransferase-to-platelet Ratio Index (APRI) is a noninvasive clinical method to assess liver fibrosis. Levels of aspartate aminotransferase and platelet counts are used to measure the APRI score, useful in patients with chronic liver disease and hepatocellular carcinoma (HCC). Recent studies have shown a link between the APRI score and various liver diseases, demonstrating its prognostic value (14, 17). 1.4 The clinical need for non-invasive markers and study rationale Understanding the correlation between APRI and ALBI scores and cancer development and prognosis, particularly CRC, helps enhance personalized healthcare approaches (16, 18). Non-invasive markers such as APRI and ALBI are essential for predicting liver function impairment and clinical decision-making, leading to patient care and therapeutic outcome improvement (16, 17). This study was designed to evaluate the correlation between APRI and ALBI indices and different stages of colorectal cancer (CRC). To the best of our knowledge, this is the first study to suggest a stage-wise comparative model for CRC considering these indices. 2. Method 2.1. Study design This study was performed as a retrospective observational study in order to assess AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in colorectal cancer patients. All the participants, across the four cancer stages, were divided into two groups: including primary stages (1 and 2) and advanced stages (3 and 4) and the two indices were compared and analyzed in both groups. This study was approved by the Ethics committee of Iran University of Medical Sciences. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. 2.2. Patient selection and study participants All patients admitted to Rasoul-e-Akram and Sina hospitals with colorectal cancer from April 2015 to 2025 and over the age of 40 were included. The criteria for inclusion were: All of primary tumors should be localized from cecum to rectum. The patient’s cancer could be categorized in one of 4 stages using biopsy and pathology report. The criteria for exclusion were: Patients with any other neoplastic disease; Combination of any other primary tumors; Patients who are receiving treatment with anti-platelet or steroid drugs. Out of 304 admitted patients, 212 met the inclusion criteria and were included in this study. 2.3. Data collection From 212 included patients pathology report and blood sample parameters were documented and extracted. The blood sample parameters were AST, platelet, albumin and total bilirubin. Using 1 week earlier biopsy reports, patients were first categorized into 4 cancer stages, according to the PTNM classification (AJCC 8th edition), and then into primary stages (including stage 1 and 2) and advanced stages (including stage 3 and 4). Two indexes were evaluated including AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI). The indexes’ formulas are shown in Fig. 1. For APRI, 0.05 and for ALBI, -2.6 are considered as cutoffs to classify groups into high and low. 2.4. Statistical analysis For each group the mean with 95% confidence interval (CI) of APRI and ALBI were calculated and compared. One way-ANOVA was used for comparison of normalized data. The odds ratio (OR) with a 95% confidence interval (CI) was computed for each index, comparing different stages. Pearson’s chi-square test and Fisher’s exact test were used to compare APRI and ALBI in each group. All statistical analyses were performed using GraphPad Prism 10.3.1. Two-tailed significance values were applied, and P < 0.05 and 95% confidence interval (CIs) were considered statistically significant. Bar charts were drawn by Graph Pad Prism 10.3.1, and the forest plot was created using RStudio version 4.3.1. 3. Results: 3.1. Patients’ characteristics Data was extracted from 212 patients between the ages of 40 to 93, all diagnosed with different stages of colorectal cancer undergoing surgical biopsy. The pathology reports from their biopsies were evaluated. Of the total cases, 57% were diagnosed with a primary-stage cancer (24% stage1, 33% stage2), and 43% of them had an advanced-stage cancer (26% stage3, 17% stage4). 3.2. Distribution of APRI and ALBI scores Chi-square test and Fisher’s exact test revealed that ALBI in the advanced-stage group, compared to the primary-stage group has an odds ratio (OR) of 1.926 with 95% confidence interval (CI) between 1.006 and 3.591. In the same way, APRI’s OR was calculated to be 3.725 and the 95% confidence interval (CI) between 1.723 and 7.783. These results show that both indices elevate significantly when the stage of cancer becomes higher compared to lower stages. The forest plot is shown in Fig. 2 . 3.3. Stage-wise comparison and correlation analysis The evaluation between different stages shows that the levels of APRI and ALBI are increased throughout the progression of the disease, but this elevation is significant when the cancer stage is the most advanced in comparison to others. As shown in Fig. 3 , the APRI level is increased in stage 4 compared to stage 3 (with a p -value of 0.0128) and stage 2 (with a p -value of 0.0115). Figure 4 shows that the ALBI level is elevated through stages 2, 3 and 4, which is the highest in stage 4. This elevation is also significant in stage4 in comparison to stage3 ( p -value = 0.03) and stage 2 ( p -value = 0.0041). 4. Discussion In this study, we explored ALBI and APRI levels in patients with colorectal cancer, through different stages. Both indexes increased as the cancer stage advanced. In stage 4, APRI and ALBI were elevated significantly in comparison to the previous stage, with p -values of 0.0128 and 0.03 respectively. No significant increases were observed between any of other stages. We also compared ALBI and APRI levels between two patient groups: those with primary-stage advanced-stage colorectal cancer. The odds ratio for ALBI was 1.926 (95% CI: 1.006–3.591), and for APRI, it was 3.725 (95% CI: 1.723–7.783). Our findings indicate that both APRI and ALBI levels rise in colorectal cancer patients, particularly in stage 4. Our results are in consistent with other studies that have evaluated APRI and ALBI in other cancers and liver dysfunction. Several studies have investigated both APRI and ALBI indices in patients with cancer or liver dysfunction. Pereyra et al. (2019) showed that in order to categorize post-chemotherapy patients by liver surgery risk, a combined assessment of both APRI and ALBI provides greater clinical value than evaluating each marker alone. They argue that this dual offers a robust framework for evaluating liver function in patients with complex clinical profiles.( 19 ) Similarly, Starlinger et al. (2021) indicated that APRI and ALBI combination assessment is more significantly associated with predicting post-hepatic resection complications, such as grade C liver dysfunction and 30-day mortality, than when each index is evaluated individually ( 20 ). APRI and ALBI are noninvasive and cost-effective indexes for evaluating liver condition, making them strong candidates to replace other tests, such as ICG clearance and ALICE. According to Santol et al. (2023), an APRI + ALBI multivariable model has a similar potential to other tests for predicting posthepatectomy liver failure (PHLF) before the surgery ( 21 ). Similarly, Mai et al. (2019) demonstrated that combined evaluation of APRI and ALBI is more prognostically valuable than their assessment alone in PHLF patients ( 22 ). In colorectal cancer patients, Zhu et al. (2020) and Kim et al. (2023) demonstrated that ALBI can be used as a prognostic tool after the surgery ( 23 , 24 ). Kim et al. (2023) stated that a combination of pre-surgery and post-surgery ALBI assessment correlates more strongly with the outcome than either assessment alone. Therefore, ALBI has the potential to guide clinical decision-making both preoperatively and postoperatively. Furthermore, another study showed that ALBI has predictive value for overall survival in esophageal cancer patients ( 25 ). ALBI index was shown to be prognostically valuable than Child-Pugh score in hepatocellular carcinoma (HCC) patients after hepatectomy by Wang et al. (2016). In this study, patients were categorized into two groups based on ALBI levels, and the group with higher ALBI had lower overall survival (OS) ( 26 ). It has been validated that elevated APRI score has a correlation with liver fibrosis, emphasizing the possible relevance to liver dysfunction in cancer patients ( 27 ). Zafar et al. (2023) showed that in esophageal carcinoma patients, APRI scores were significantly correlated with clinical and clinicopathological features and survival of the disease ( 28 ). Several studies have explored APRI levels in patients with hepatocellular carcinoma (HCC) after liver resection. Mai et al. (2019) and Shu et al. (2023) demonstrated that by using APRI scoring system we can predict post-surgery outcomes in HCC patients. APRI was found to have stronger correlations with the outcome than MELD, ALBI, Child-Pugh scores ( 29 , 30 ). These two indices have been stablished to be prognostic tools to predict liver metastasis in different metastasis including colorectal cancer (CRC). ALBI has been assessed as an index to predict mortality and overall survival (OS) in patients with colorectal cancer (CRC) ( 31 , 32 ). Also, Hu et al. (2020) suggested that APRI, as a liver fibrosis indicator, is an effective prognostic marker to predict hepatic metastasis and reccurence in CRC patients ( 33 ). Other studies have explored the importance of the indexes in liver metastasis prediction in patients with breast cancer and pancreatic cancer ( 34 , 35 ). No study has explored APRI and ALBI levels across different stages of colorectal cancer (CRC), thus we aimed to do a stage-wise analysis and a comparison between high-risk and low-risk patients. However, our study is not without limitations. The retrospective nature of the research introduces selection bias, and the single-center design limits the generalizability of the results. In addition, there is a lack of standardized cut-off values for both indices, which should be addressed in future studies. In the current research, we did not have access to clinicopathological data such as BMI, medical history, lifestyle habits, diabetes status, hypertension, and other variables that may influence outcomes. Further studies are needed to incorporate these factors into similar analyses. While our results may be applicable to other populations, this should be interpreted with caution, considering differences in lifestyle and demographic characteristics. APRI and ALBI are two examples of noninvasive and cost-effective markers for evaluating liver function and assisting in clinical decision-making. Therefore, further research is needed to develop a unified framework that supports both physicians and patients in managing colorectal cancer. 5. Conclusion In conclusion, our study investigated the levels of APRI and ALBI in 4 stages of colorectal cancer (CRC) and compared each group. The findings suggest that both indices increase as the cancer progresses, and in stage 4, a significant increase is seen. Comparison of advanced and primary stages of cancer revealed that high levels of both indices are highly associated with the advanced stages. These easy-to-use, noninvasive markers are great tools to evaluate patients’ condition and make clinical decisions, thereby further research in this area is needed. Abbreviations Colorectal cancer = CRC Aspartate transaminase = AST AST to platelet ratio index = APRI Albumin-bilirubin score = ALBI Hepatocellular carcinoma = HCC Overall survival = OS Non-alcoholic fatty liver disease = NAFLD Confidence interval = CI Odds ratio = OR Standard error of the mean = SEM Declarations Ethics approval and consent to participate It is hereby announced that informed consent has been obtained from all the participants to conduct the study and the personal information of the patients will not be disclosed in any way. The patient consent form is the official form of Rasool-e-Akram and Sina Hospitals and is available for all patients. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare no competing interests. Funding This study was not financially supported. Authors' contributions All authors have made significant contributions to this study. B.S.A designed the work, collected some data, performed the statistical analyses, and prepared the final manuscript. H.R supervised the implementation of the plan. M.S.B collected some data, and wrote a part of the main manuscript text. Y.R collected some data and wrote a part of the main manuscript text. A.S supervised the implementation of the plan and edited the main manuscript text. A.G wrote a part of the main manuscript text. Acknowledgements We extend our sincere appreciation to Rasool-e-Akram and Sina Hospitals and their dedicated staff for their invaluable support and collaboration throughout this study. References Rezazadeh M, Agah S, Kamyabi A, Akbari A, Ghamkhari Pisheh R, Eshraghi A, et al. Effect of diabetes mellitus type 2 and sulfonylurea on colorectal cancer development: a case-control study. BMC Gastroenterology. 2024;24(1):382. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7426295","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":521668687,"identity":"de25c2de-9198-4b0e-9a57-21140db4bcbb","order_by":0,"name":"Bahareh Shateri Amiri","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Bahareh","middleName":"Shateri","lastName":"Amiri","suffix":""},{"id":521668688,"identity":"d677a419-8fa0-4e4c-b8f4-333faf0f89fd","order_by":1,"name":"Mohammad Sadegh Bazgoshaeyan","email":"","orcid":"","institution":"Iran University of 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1","display":"","copyAsset":false,"role":"figure","size":41229,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7426295/v1/9932ab91c1ba7c2d173683a5.png"},{"id":92474662,"identity":"a0709f5d-bde1-4e4a-a066-eabf3118bff2","added_by":"auto","created_at":"2025-09-30 07:13:09","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42260,"visible":true,"origin":"","legend":"\u003cp\u003eALBI and APRI distribution in different groups of colorectal cancer patients\u003c/p\u003e","description":"","filename":"figure2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7426295/v1/c01b702b2d1ee8dece17e693.jpeg"},{"id":92474665,"identity":"e83b5f47-9200-4e46-b413-53db911ed944","added_by":"auto","created_at":"2025-09-30 07:13:09","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":75541,"visible":true,"origin":"","legend":"\u003cp\u003eAPRI levels in each stage (Mean + SEM is calculated. *p\u0026lt;0.05)\u003c/p\u003e","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7426295/v1/2118fc36b2a8fc25ce0d691e.jpg"},{"id":92474698,"identity":"c5903339-619e-4313-8267-cf410ed88c05","added_by":"auto","created_at":"2025-09-30 07:13:10","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":84911,"visible":true,"origin":"","legend":"\u003cp\u003eALBI levels in each stage (Mean + SEM is calculated. *p\u0026lt;0.05, **p\u0026lt;0.01)\u003c/p\u003e","description":"","filename":"figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7426295/v1/b177bff2fe1f087d8d1086b5.jpg"},{"id":92478311,"identity":"257e7abe-af0e-4f33-b2d4-e788f200f930","added_by":"auto","created_at":"2025-09-30 07:29:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":867025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7426295/v1/43c0a0e1-1cc6-450b-b483-33e8b9b9d7e1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in patients with colorectal cancer: A stage-wise analysis","fulltext":[{"header":"1.\tIntroduction","content":"\u003cp\u003e\u003cstrong\u003e1.1 Background on CRC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eColorectal cancer (CRC) ranks as the third most prevalent cancer worldwide and is the second leading cause of cancer-related mortality, resulting in approximately 600,000 deaths each year (1, 2). It is estimated that CRC cases will increase to 3.2 million, with mortality rising to 1.6 million by 2040 (3).\u0026nbsp;There remains an urgent need for further investigation into noninvasive biomarkers for early diagnosis, as well as the discovery of innovative therapeutic targets for CRC\u0026nbsp;(4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.2 Hepatic dysfunction and metastasis in CRC and its evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSome of the most challenging complications of colorectal cancer (CRC) are hepatic dysfunction and metastasis, which create difficulties in treating this prevalent malignancy. Liver metastasis is common in nearly 20-50% of CRC cases, is significantly associated with disease-related mortality (5, 6). \u0026nbsp;Due to vast vascular connection with the gastrointestinal tract, the liver is the most common site of distant metastasis with tumors spreading through the portal vein (7, 8). Furthermore, chronic inflammation, such as non-alcoholic fatty liver disease (NAFLD), has been shown to elevate the risk of liver metastasis (9). Predicting liver metastases by evaluating systemic inflammatory markers has received attention, especially systemic immune-inflammatory index (10). Moreover, novel biomarkers, including specific microRNAs, show potential in evaluating metastasis risk and therapeutic response (11).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.3 Introduction to ALBI and APRI score\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe albumin-bilirubin (ALBI) score is a clinical scoring system, including two routine blood test parameters: serum albumin and total bilirubin levels, which is used to evaluate the liver function, especially in patients with hepatocellular carcinoma (HCC) and other liver-related conditions (12-14).\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eIt should be noted that research has shown a significant correlation between ALBI score and prognostic outcomes in various cancers, including colorectal cancer (CRC). It has been shown that higher baseline scores indicate poorer overall survival (OS) and progression-free survival (PFS)\u0026nbsp;(14-16). Additionally, the preoperative ALBI score has been established as a substantial predictor of immediate outcomes following radical surgery\u0026nbsp;(15, 16). Studies have shown ALBI score can be used in patients with liver metastases to assess function of the liver and overall prognosis\u0026nbsp;(15).\u003c/p\u003e\n\u003cp\u003eThe Aspartate Aminotransferase-to-platelet Ratio Index (APRI) is a noninvasive clinical method to assess liver fibrosis. Levels of aspartate aminotransferase and platelet counts are used to measure the APRI score, useful in patients with chronic liver disease and hepatocellular carcinoma (HCC). Recent studies have shown a link between the APRI score and various liver diseases, demonstrating its prognostic value (14, 17).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.4 The clinical need for non-invasive markers and study rationale\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnderstanding the correlation between APRI and ALBI scores and cancer development and prognosis, particularly CRC, helps enhance personalized healthcare approaches (16, 18). Non-invasive markers such as APRI and ALBI are essential for predicting liver function impairment and clinical decision-making, leading to patient care and therapeutic outcome improvement (16, 17).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study was designed to evaluate the correlation between APRI and ALBI indices and different stages of colorectal cancer (CRC). To the best of our knowledge, this is the first study to suggest a stage-wise comparative model for CRC considering these indices. \u0026nbsp;\u003c/p\u003e"},{"header":"2. Method","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Study design\u003c/h2\u003e\u003cp\u003eThis study was performed as a retrospective observational study in order to assess AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in colorectal cancer patients. All the participants, across the four cancer stages, were divided into two groups: including primary stages (1 and 2) and advanced stages (3 and 4) and the two indices were compared and analyzed in both groups. This study was approved by the Ethics committee of Iran University of Medical Sciences. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Patient selection and study participants\u003c/h2\u003e\u003cp\u003eAll patients admitted to Rasoul-e-Akram and Sina hospitals with colorectal cancer from April 2015 to 2025 and over the age of 40 were included.\u003c/p\u003e\u003cp\u003eThe criteria for inclusion were: All of primary tumors should be localized from cecum to rectum. The patient\u0026rsquo;s cancer could be categorized in one of 4 stages using biopsy and pathology report.\u003c/p\u003e\u003cp\u003eThe criteria for exclusion were: Patients with any other neoplastic disease; Combination of any other primary tumors; Patients who are receiving treatment with anti-platelet or steroid drugs.\u003c/p\u003e\u003cp\u003eOut of 304 admitted patients, 212 met the inclusion criteria and were included in this study.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Data collection\u003c/h2\u003e\u003cp\u003eFrom 212 included patients pathology report and blood sample parameters were documented and extracted. The blood sample parameters were AST, platelet, albumin and total bilirubin.\u003c/p\u003e\u003cp\u003eUsing 1 week earlier biopsy reports, patients were first categorized into 4 cancer stages, according to the PTNM classification (AJCC 8th edition), and then into primary stages (including stage 1 and 2) and advanced stages (including stage 3 and 4).\u003c/p\u003e\u003cp\u003eTwo indexes were evaluated including AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI). The indexes\u0026rsquo; formulas are shown in Fig.\u0026nbsp;1. For APRI, 0.05 and for ALBI, -2.6 are considered as cutoffs to classify groups into high and low.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e\u003cp\u003eFor each group the mean with 95% confidence interval (CI) of APRI and ALBI were calculated and compared. One way-ANOVA was used for comparison of normalized data. The odds ratio (OR) with a 95% confidence interval (CI) was computed for each index, comparing different stages. Pearson\u0026rsquo;s chi-square test and Fisher\u0026rsquo;s exact test were used to compare APRI and ALBI in each group. All statistical analyses were performed using GraphPad Prism 10.3.1. Two-tailed significance values were applied, and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and 95% confidence interval (CIs) were considered statistically significant. Bar charts were drawn by Graph Pad Prism 10.3.1, and the forest plot was created using RStudio version 4.3.1.\u003c/p\u003e"},{"header":"3. Results:","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Patients\u0026rsquo; characteristics\u003c/h2\u003e\u003cp\u003eData was extracted from 212 patients between the ages of 40 to 93, all diagnosed with different stages of colorectal cancer undergoing surgical biopsy. The pathology reports from their biopsies were evaluated. Of the total cases, 57% were diagnosed with a primary-stage cancer (24% stage1, 33% stage2), and 43% of them had an advanced-stage cancer (26% stage3, 17% stage4).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Distribution of APRI and ALBI scores\u003c/h2\u003e\u003cp\u003eChi-square test and Fisher\u0026rsquo;s exact test revealed that ALBI in the advanced-stage group, compared to the primary-stage group has an odds ratio (OR) of 1.926 with 95% confidence interval (CI) between 1.006 and 3.591. In the same way, APRI\u0026rsquo;s OR was calculated to be 3.725 and the 95% confidence interval (CI) between 1.723 and 7.783. These results show that both indices elevate significantly when the stage of cancer becomes higher compared to lower stages. The forest plot is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Stage-wise comparison and correlation analysis\u003c/h2\u003e\u003cp\u003eThe evaluation between different stages shows that the levels of APRI and ALBI are increased throughout the progression of the disease, but this elevation is significant when the cancer stage is the most advanced in comparison to others. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the APRI level is increased in stage 4 compared to stage 3 (with a \u003cem\u003ep\u003c/em\u003e-value of 0.0128) and stage 2 (with a \u003cem\u003ep\u003c/em\u003e-value of 0.0115).\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows that the ALBI level is elevated through stages 2, 3 and 4, which is the highest in stage 4. This elevation is also significant in stage4 in comparison to stage3 (\u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.03) and stage 2 (\u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.0041).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this study, we explored ALBI and APRI levels in patients with colorectal cancer, through different stages. Both indexes increased as the cancer stage advanced. In stage 4, APRI and ALBI were elevated significantly in comparison to the previous stage, with \u003cem\u003ep\u003c/em\u003e-values of 0.0128 and 0.03 respectively. No significant increases were observed between any of other stages. We also compared ALBI and APRI levels between two patient groups: those with primary-stage advanced-stage colorectal cancer. The odds ratio for ALBI was 1.926 (95% CI: 1.006\u0026ndash;3.591), and for APRI, it was 3.725 (95% CI: 1.723\u0026ndash;7.783). Our findings indicate that both APRI and ALBI levels rise in colorectal cancer patients, particularly in stage 4.\u003c/p\u003e\u003cp\u003eOur results are in consistent with other studies that have evaluated APRI and ALBI in other cancers and liver dysfunction. Several studies have investigated both APRI and ALBI indices in patients with cancer or liver dysfunction. Pereyra et al. (2019) showed that in order to categorize post-chemotherapy patients by liver surgery risk, a combined assessment of both APRI and ALBI provides greater clinical value than evaluating each marker alone. They argue that this dual offers a robust framework for evaluating liver function in patients with complex clinical profiles.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eSimilarly, Starlinger et al. (2021) indicated that APRI and ALBI combination assessment is more significantly associated with predicting post-hepatic resection complications, such as grade C liver dysfunction and 30-day mortality, than when each index is evaluated individually (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAPRI and ALBI are noninvasive and cost-effective indexes for evaluating liver condition, making them strong candidates to replace other tests, such as ICG clearance and ALICE. According to Santol et al. (2023), an APRI\u0026thinsp;+\u0026thinsp;ALBI multivariable model has a similar potential to other tests for predicting posthepatectomy liver failure (PHLF) before the surgery (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Similarly, Mai et al. (2019) demonstrated that combined evaluation of APRI and ALBI is more prognostically valuable than their assessment alone in PHLF patients (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn colorectal cancer patients, Zhu et al. (2020) and Kim et al. (2023) demonstrated that ALBI can be used as a prognostic tool after the surgery (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Kim et al. (2023) stated that a combination of pre-surgery and post-surgery ALBI assessment correlates more strongly with the outcome than either assessment alone. Therefore, ALBI has the potential to guide clinical decision-making both preoperatively and postoperatively. Furthermore, another study showed that ALBI has predictive value for overall survival in esophageal cancer patients (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eALBI index was shown to be prognostically valuable than Child-Pugh score in hepatocellular carcinoma (HCC) patients after hepatectomy by Wang et al. (2016). In this study, patients were categorized into two groups based on ALBI levels, and the group with higher ALBI had lower overall survival (OS) (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIt has been validated that elevated APRI score has a correlation with liver fibrosis, emphasizing the possible relevance to liver dysfunction in cancer patients (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Zafar et al. (2023) showed that in esophageal carcinoma patients, APRI scores were significantly correlated with clinical and clinicopathological features and survival of the disease (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Several studies have explored APRI levels in patients with hepatocellular carcinoma (HCC) after liver resection. Mai et al. (2019) and Shu et al. (2023) demonstrated that by using APRI scoring system we can predict post-surgery outcomes in HCC patients. APRI was found to have stronger correlations with the outcome than MELD, ALBI, Child-Pugh scores (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThese two indices have been stablished to be prognostic tools to predict liver metastasis in different metastasis including colorectal cancer (CRC). ALBI has been assessed as an index to predict mortality and overall survival (OS) in patients with colorectal cancer (CRC) (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Also, Hu et al. (2020) suggested that APRI, as a liver fibrosis indicator, is an effective prognostic marker to predict hepatic metastasis and reccurence in CRC patients (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Other studies have explored the importance of the indexes in liver metastasis prediction in patients with breast cancer and pancreatic cancer (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNo study has explored APRI and ALBI levels across different stages of colorectal cancer (CRC), thus we aimed to do a stage-wise analysis and a comparison between high-risk and low-risk patients.\u003c/p\u003e\u003cp\u003eHowever, our study is not without limitations. The retrospective nature of the research introduces selection bias, and the single-center design limits the generalizability of the results. In addition, there is a lack of standardized cut-off values for both indices, which should be addressed in future studies.\u003c/p\u003e\u003cp\u003eIn the current research, we did not have access to clinicopathological data such as BMI, medical history, lifestyle habits, diabetes status, hypertension, and other variables that may influence outcomes. Further studies are needed to incorporate these factors into similar analyses. While our results may be applicable to other populations, this should be interpreted with caution, considering differences in lifestyle and demographic characteristics.\u003c/p\u003e\u003cp\u003eAPRI and ALBI are two examples of noninvasive and cost-effective markers for evaluating liver function and assisting in clinical decision-making. Therefore, further research is needed to develop a unified framework that supports both physicians and patients in managing colorectal cancer.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, our study investigated the levels of APRI and ALBI in 4 stages of colorectal cancer (CRC) and compared each group. The findings suggest that both indices increase as the cancer progresses, and in stage 4, a significant increase is seen. Comparison of advanced and primary stages of cancer revealed that high levels of both indices are highly associated with the advanced stages. These easy-to-use, noninvasive markers are great tools to evaluate patients\u0026rsquo; condition and make clinical decisions, thereby further research in this area is needed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eColorectal cancer = CRC\u003c/p\u003e\n\u003cp\u003eAspartate transaminase = AST\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAST to platelet ratio index = APRI\u003c/p\u003e\n\u003cp\u003eAlbumin-bilirubin score = ALBI\u003c/p\u003e\n\u003cp\u003eHepatocellular carcinoma = HCC\u003c/p\u003e\n\u003cp\u003eOverall survival = OS\u003c/p\u003e\n\u003cp\u003eNon-alcoholic fatty liver disease = NAFLD\u003c/p\u003e\n\u003cp\u003eConfidence interval = CI\u003c/p\u003e\n\u003cp\u003eOdds ratio = OR\u003c/p\u003e\n\u003cp\u003eStandard error of the mean = SEM\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt is hereby announced that informed consent has been obtained from all the participants to conduct the study and the personal information of the patients will not be disclosed in any way. The patient consent form is the official form of Rasool-e-Akram and Sina Hospitals and is available for all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not financially supported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have made significant contributions to this study. B.S.A designed the work, collected some data, performed the statistical analyses, and prepared the final manuscript. H.R supervised the implementation of the plan. M.S.B collected some data, and wrote a part of the main manuscript text. Y.R collected some data and wrote a part of the main manuscript text. A.S supervised the implementation of the plan and edited the main manuscript text. A.G wrote a part of the main manuscript text.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extend our sincere appreciation to Rasool-e-Akram and Sina Hospitals and their dedicated staff for their invaluable support and collaboration throughout this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRezazadeh M, Agah S, Kamyabi A, Akbari A, Ghamkhari Pisheh R, Eshraghi A, et al. Effect of diabetes mellitus type 2 and sulfonylurea on colorectal cancer development: a case-control study. 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Pathol Oncol Res. 2023;29:1611175.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7426295/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7426295/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eColorectal cancer (CRC) is the third most common malignancy globally and a leading cause of cancer-related death. Liver dysfunction and metastasis remain major contributors to poor outcomes. Noninvasive biomarkers such as the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) and the Albumin-Bilirubin (ALBI) score have shown potential in assessing liver function and predicting prognosis, but their stage-wise relevance in CRC is not well established.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eThis retrospective observational study included 212 CRC patients aged\u0026thinsp;\u0026ge;\u0026thinsp;40 years admitted to Rasoul-e-Akram and Sina hospitals between 2015 and 2025. Patients were categorized into primary (stages 1 and 2) and advanced (stages 3 and 4) groups. APRI and ALBI scores were calculated from blood parameters and compared across stages using one-way ANOVA, chi-square, and Fisher\u0026rsquo;s exact tests. Odds ratios (OR) with 95% confidence intervals (CI) were computed, with \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eOf the included patients, 57% had primary-stage CRC and 43% advanced-stage CRC. Both APRI and ALBI scores increased significantly with advancing cancer stage. Compared with primary stages, APRI showed an OR of 3.725 (95% CI: 1.723\u0026ndash;7.783) and ALBI an OR of 1.926 (95% CI: 1.006\u0026ndash;3.591) for advanced disease. Stage-wise analysis revealed that APRI (\u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.0128) and ALBI (\u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.03) were significantly higher in stage 4 compared to stage 3, with similar differences observed against earlier stages.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eAPRI and ALBI scores increase with CRC progression, with the most pronounced elevations in stage 4. These indices offer simple, noninvasive, and cost-effective tools for assessing disease severity and guiding clinical decision-making. Prospective multicenter studies are needed to validate their prognostic utility and to establish standardized cut-off values.\u003c/p\u003e","manuscriptTitle":"Assessment of AST to platelet ratio index (APRI) and albumin-bilirubin score (ALBI) in patients with colorectal cancer: A stage-wise analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-30 07:13:04","doi":"10.21203/rs.3.rs-7426295/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-09-30T21:46:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139939133457905814776580336587015385035","date":"2025-09-30T21:08:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232710549717781995325587843960709539646","date":"2025-09-22T08:12:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-18T05:47:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-28T19:47:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-26T05:54:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-26T05:53:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-08-21T12:34:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d551af76-1a43-4a13-86c5-8daf405161ba","owner":[],"postedDate":"September 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-30T07:13:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-30 07:13:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7426295","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7426295","identity":"rs-7426295","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}