Prognostic and Immunological Implications of FAM72A in Pan-Cancer and Functional Validations

Abstract

The family with sequence similarity 72 Member A (FAM72A) is overexpressed in several types of cancer. However, its contributions to tumorigenesis remain largely unknown. Based on The Cancer Genome Atlas (TCGA) database, FAM72A was upregulated across 33 types of cancer. Accordingly, high levels of FAM72A predicted inferior outcomes in half of the cancer types using survival analysis (the Kaplan-Meier curve and univariate Cox regression model). Receiver operating characteristic (ROC) analysis demonstrated that FAM72A showed high accuracy in distinguishing cancerous tissues from normal ones. FAM72A was correlated with immune and stromal scores and immune cell infiltrations in various tumors. Moreover, FAM72A was also associated with tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes. Immunophenoscore (IPS) further validated that the FAM72Alow tumor showed high immunogenicity and tended to respond to anti-PD1/PDL1/PDL2, anti-CTLA4 treatment, and combined immunotherapies. We also investigated the functional role of FAM72A in lung adenocarcinoma (LUAD). In vitro studies demonstrated that the ectopic expression of FAM72A accelerated the proliferation and migration of NSCLC cells, whereas silencing FAM72A showed the opposite effects on them. In short, FAM72A had prognostic potential and correlated with tumor immunogenicity in various tumors. Functional analysis indicated that FAM72A is an oncogene in LUAD.

PVALB Was Identified as an Independent Prognostic Factor for HCC Closely Related to Immunity, and Its Absence Accelerates Tumor Progression by Regulating NK Cell Infiltration

“…In addition, the 3 most correlated genes were presented in scatter plots, which were CD244 (R=0.403, p<0.001), TIGIT (R=0.400, p<0.001), CD96 (R=0.375, p<0.001) ( Figure 9C–E ). As a critical tumor feature, MSI may be connected with the reaction to immunotherapy, 45 therefore, we probed the link between PVALB expression and MSI score in HCC. It was revealed that the two maintained a negative correlation, suggesting that the probability of mutation was higher when PVALB was lowly expressed in HCC, at which time a better result was achieved with immunotherapy ( Figure 9F ).…”