AUTHOR=Ding Xinjiang , Yao Tao , Liu Xi , Fan Zhongwen , Liu Yuanxing TITLE=A macropinocytosis-related gene signature predicts the prognosis and immune microenvironment in hepatocellular carcinoma JOURNAL=Frontiers in Oncology VOLUME=Volume 13 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1143013 DOI=10.3389/fonc.2023.1143013 ISSN=2234-943X ABSTRACT=Background: Available treatments for hepatocellular carcinoma (HCC), a common human malignancy with a low survival rate, remain unsatisfactory. Macropinocytosis (MPC), a type of endocytosis that involves the nonspecific uptake of dissolved molecules, is shown to contribute to HCC pathology; however, its biological mechanism remains unknown. Methods: The current study identified 27 MRGs from 71 candidate genes using bioinformatics. R software was used to conduct to create a prognostic signature model by filtering standardized mRNA expression data from HCC patients and using various methods to verify the reliability of the model and indicate immune activity. Results: The prognostic signature was constructed using seven MPC-related differentially expressed genes (MRGs), GSK3B, AXIN1, RAC1, KEAP1, EHD1, GRB2, and SNX5, through LASSO Cox regression. The risk score was acquired from the expression of these genes and their corresponding coefficients. HCC patients in the discovery and validation cohorts were stratified and the survival of low-risk-score patients was improved in both cohorts. Time-dependent ROC analysis indicated that the model’s prediction reliability was highest in the short term. Subsequent immunologic analysis, including KEGG, located the immune action pathway of the differentially expressed genes in the direction of the cancer pathway etc. Immune infiltration and immune checkpoint tests provided valuable guidance for future follow-up experiments Conclusion: A risk model with MRGs was constructed to effectively predict HCC patient prognoses and suggest changes in the immune microenvironment during the disease process. The findings should benefit the development of a prognostic stratification and treatment strategy for HCC.