The pan-cancer analysis reveals FAM72D as a potential therapeutic target and closely linked to immune infiltration and prognosis in hepatocellular carcinoma

Abstract

Abstract Background: FAM72D, a gene that is rarely reported, and its effects in tumors remain elusive. A similar lack of association between its expression and tumor progression, immune microenvironment, and prognosis has been reported. The present study aims to provide a comprehensive landscape view of FAM72D in tumorigenesis, prognosis, and correlation with the tumor microenvironment (TME). Method: We obtained the gene expression profiles of FAM72D from TCGA (https://xenabrowser.net or https://portal. gdc.cancer.gov/) database. The cBioPortal online database and TIMER2.0 were used to analyze the prognosis, immune infiltration, mutational landscape, and molecular function of FAM72D in pan-cancer. A protein-protein interaction network was performed to identify hub genes, and Gene Ontology (GO) analysis was used to identify relevant signaling pathways in pan-cancer. We constructed a risk score model in hepatocellular carcinoma (HCC) and validated it in ICGC (International Cancer Genome Consortium). Meanwhile, sensitivity analyses of some common chemotherapeutic agents and targeted drugs were also analyzed. RT qPCR was used to analyze FAM72D expression differences in Huh7 and LO2 cell lines. Results: FAM72D expression was significantly upregulated in various tumors compared with adjacent noncancerous tissues in pan-cancer. Elevated expression of FAM72D is correlated with poor prognosis. Genetic alterations in FAM72D affect disease free survival (DFS) in pan-cancer. In most cancers, high levels of FAM72D were associated with infiltration of myeloid-derived suppressor cells (MDSCs), CD4+ Th1 and Th2 cells. It was found that FAM72D had an association with cell growth and energy metabolism based on GO analysis. FAM72D similarly affects cell cycle, differentiation, and inflammatory in some tumors. In HCC, based on FAM72D associated differentially expressed genes (DEGs), a prognostic signature of 4 genes was constructed to predict prognosis. Chemotherapeutic or targeted agents suitable for different risk groups of HCC were also screened. Additionally, FAM72D is associated with metastasis and proliferation of HCC. FAM72D is a potential biomarker of tumor prognosis, molecular and immune microenvironment. Conclusion: Our study shows that FAM72D is involved in the carcinogenesis in various tumors while affecting prognosis and immune cell infiltration. FAM72D may serve as a reliable biomarker for the prognosis of several tumors. Meanwhile, this study shed new light on for the treatment of HCC.