Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model

Abstract FRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed FRG1 expression is associated with the overall survival (OS) in cancers the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 expression groups, but in breast, lung, and liver cancers the difference was not prominent. We hypothesized that the functionality of the genes correlated with FRG1 could be getting affected by FRG1 or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, and HIPPIE were used to deduce FRG1 associated pathways. In breast, lung, and liver cancer we found a distinct difference in the OS, between the low and high FRG1 expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups revealed a significant difference in the FRG1 expression and survival. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 expression on these genes by qRT-PCR, supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.