The role of YAP1 in survival prediction, immune modulation, and drug response: A pan-cancer perspective

Dysregulation of the Hippo signaling pathway has been implicated in multiple pathologies, including cancer, and is the major effector of the pathway. In this study, we assessed the role of in prognostic value, immunomodulation, and drug response from a pan-cancer perspective. We compared expression between normal and cancerous tissues and among different pathologic stages survival analysis and gene set enrichment analysis were performed. Additionally, we performed correlation analyses of expression with RNA modification-related gene expression, tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint regulator expression, and infiltration of immune cells. Correlations between expression and IC s (half-maximal inhibitory concentrations) of drugs in the CellMiner database were calculated. We found that was aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications, particularly m6A methylation. High expression of was associated with poor survival outcomes in ACC, BLCA, LGG, LUAD, and PAAD. expression was negatively correlated with the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, and positively correlated with the infiltration of myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in pan-cancer. Higher expression showed upregulation of TGF-β signaling, Hedgehog signaling, and KRAS signaling. IC s of FDA-approved chemotherapeutic drugs capable of inhibiting DNA synthesis, including teniposide, dacarbazine, and doxorubicin, as well as inhibitors of hypoxia-inducible factor, MCL-1, ribonucleotide reductase, and FASN in clinical trials were negatively correlated with expression. In conclusion, is aberrantly expressed in various cancer types and regulated by its DNA methylation and post-transcriptional modifications. High expression of is associated with poor survival outcomes in certain cancer types. YAP1 may promote tumor progression through immunosuppression, particularly by suppressing the infiltration of CD8+ T lymphocytes, CD4+ Th1 cells, T follicular helper cells, NKT cells, and activated NK cells, as well as recruiting MDSCs and CAFs in pan-cancer. The tumor-promoting activity of is attributed to the activation of TGF-β, Hedgehog, and KRAS signaling pathways. AZD2858 and varlitinib might be effective in cancer patients with high expression.