Role and mechanism of YAP1 in pan-cancer

Abstract Backgrounds and aims: Cancers threaten health and life of patients with tumors. It is important to diagnose and treat various tumors as early as possible. However, there is limited early biomarkers for cancers. Yes-associated protein 1 (Yap1) is involved in the Hippo signaling pathway, and thus regulating development and cell growth. Yap1’s role in pan-cancer remains to be investigated. The objective of the present investigation was to explore the possible role and mechanism of Yap1 in pan-cancer. Methods Timer2.0 and GEPIA were employed to analyze the expression of YAP1 in cancerous tissues and controls; HPA was used to study the expression of YAP1 in different tissues and subcellular location; for survival analysis, GEPIA, the HPA, and KM plotter were utilized to generate survival curves, evaluating the prognostic significance of YAP1 expression; cBioPortal was used to investigate the mutation frequency and genetic alterations of YAP1; AlphaFold was applied to predict the structure of Yap1 and identify potential pathogenic sites, while PhosphoNet helped in predicting and analyzing phosphorylation sites of Yap1; the STRING was employed to explore Yap1's interacting proteins. Results The levels of YAP1 in tumor tissues were mostly lower than controls; Yap1 was ubiquitously expressed and located in cytosol; YAP1 is a significant predictor of survival in PAAD and KIRC; its expression is closely linked to immune infiltration; YAP1 exhibits a high mutation frequency across various cancer types; many phosphorylation sites especially S276 in Yap1 is highly a phosphorylation site; Yap1 interacts with proteins including Last1 and Last2 associated with the hypoxia pathway. Conclusion Yap1 is significantly associated with pan-cancer, which may serve as a potential biomarker of cancers.