Deciphering the Prognostic Implications of T Cell Marker Gene Signatures in Hepatocellular Carcinoma Tumor Microenvironment

Abstract

Background: Hepatocellular carcinoma is a kind of cancer that begins in the liver and has a high recurrence and death rate. It has been shown that hepatocellular carcinoma patients who get treatment with novel immunotherapy that targets the tumor microenvironment have better survival rates than those who do not. However, not all patients with Hepatocellular Carcinoma respond well to immunotherapy due to a lack of knowledge about the tumor microenvironment. Methods: Hepatocellular carcinoma patients with infiltrated immune cells had a better prognosis, as determined by MCP-counter algorithms. To further understand the role of T cell markers in hepatocellular cancer, researchers sequenced the RNA of individual cells (GSE146115). T cell marker genes (TCMS) were constructed and validated using data from GSE10141, GSE14520, and The Cancer Genome Atlas-liver hepatocellular carcinoma. Results: Those with hepatocellular carcinoma who had T cells infiltrating their tumors had a better chance of surviving the disease, as shown by the survival study. The genes Helicase With Zinc Finger (HELZ), Granzyme A (GZMA), Solute Carrier Family 2 Member 2 (SLC2A2), and Janus Kinase 3 (JAK3) are four T cell marker genes accounted for in the TCMS model. Patients with hepatocellular carcinoma may be divided into high- and low-risk categories based on their TCMS scores. In a multivariate analysis of data from The Cancer Genome Atlas validation cohort, the TCMS risk score remained a significant determinant in overall survival. High levels of CD8+ T cell, and CD4+ T cell infiltration were also substantially linked with elevated expression of HELZ, GZMA, and JAK3. Conclusions: Successfully constructing the T cell marker genes profile with strong predictive function, we also presented a unique perspective on T cell infiltration in the tumor microenvironment, which may give guidelines for clinical application in Hepatocellular carcinoma immunotherapy.