Functional Significance of SIGLECs Family in HCC and its Predictive Role in HCC Patients Undergoing Sorafenib

Background and Aims: Hepatocellular carcinoma (HCC) is an aggressively malignant type of cancer with a complex pathogenesis. For HCC patients, there is not only a deficiency of valuable therapeutic targets but also a deficiency of prognostic biomarkers. Although some progress has been made in the immunotherapy of HCC, sorafenib remains one of the irreplaceable therapeutic for advanced HCC patients. However, after 10 years of exploration on sorafenib clinical application, there are still no confirmed prognostic factors of therapeutic effect. Methods: The clinical significance and molecular work of the SIGLEC family were assessed by comprehensive bioinformatic analysis.The TCGA, GEO and HCCDB databases were used to explore the expression of SIGLEC family genes in HCC. The Kaplan-Meier Plotter database was analysed to discover the connection between SIGLEC family genes and prognosis of patients. Besides, possible connections between differentially expressed genes (DEGs) of SIGLEC family and tumor-associated immunity were evaluated using TIMER. Results: The outcomes showed that the mRNA levels of most SIGLEC family genes were significantly down-regulated in HCC compared with normal tissues. Low protein and mRNA expression of SIGLECs were found to be considerably correlated with tumor grade and clinical cancer stages in HCC patients. Tumor related SIGLECs family genes were associated with tumor immune infiltrating cell. To our surprise, the high expression of SIGLECs family is significantly related with the better prognosis of HCC patients treated with sorafenib. Conclusions: In conclusion, SIGLEC family genes have considerable prognostic value in HCC and they may play main roles in regulating cancer progress and the immune cell infiltration. More importantly, we revealed that SIGLEC family genes may become a predictive index for the efficacy evaluation of sorafenib someday.