Eight-Gene Metabolic Signature Related with Tumor-Associated Macrophages Predicting Overall Survival for Hepatocellular Carcinoma

Abstract Background: In recent years, the relationship between tumor associated macrophages (TAMs) and solid tumors has become a research hotspot. The study aims at exploring the close relationship of TAMs with metabolic reprogramming genes in hepatocellular carcinoma(HCC), in order to provide a new way of treatment for HCC.Materials and methods: The study selected 343 HCC patients with complete survival information(survival time >= 1month) in the Cancer Genome Atlas (TCGA) as the study objects. Kaplan-Meier survival analysis assisted in figuring out the relationship between macrophage infiltration level and overall survival (OS), and Pearson correlation test to identify metabolic reprogramming genes(MRGs) related to tumor macrophage abundance. Lasso regression algorithm were conducted on prognosis related MRGs screened by Univariate Cox regression analysis and Kaplan-Meier survival analysis to construct the riskscore, another independent cohort (including 228 HCC patients) from the International Cancer Genome Consortium (ICGC) were used for external validation regarding the prognostic signature.Results: A risk score composed of 8 metabolic genes can accurately predict the OS of training cohort(TCGA) and testing cohort(ICGC). It is important that the risk score could widely used for people with different clinical characteristics, and is an independent predictor independent of other clinical factors affecting prognosis. As expected, high-risk group exhibited an obviously higher macrophage abundance relative to low-risk group, and the risk score presented a positive relation to the expression level of three commonly used immune checkpoints(PD1,PDL1,CTLA4).Conclusion: Our study constructed and validated a novel eight‑gene signature for predicting HCC patients’ OS, which possibly contributed to making clinical treatment decisions.