The Prognostic Impact of SIRT1, STAT3, and YAP1 in Colorectal Carcinoma.

Abstract

Colorectal cancer (CRC) is the most common gastrointestinal malignancy with a complicated behavior including relapse, metastasis, and development of resistance to chemotherapeutic drugs. Silent information regulator 2 homologue 1 (SIRT1), signal transducer and activator of transcription 3 (STAT3), and yes-associated protein (YAP) are cancer-related genes that have unclarified actions and even controversial roles in many human cancers including CRC. The current study aimed to evaluate the prognostic roles of SIRT1, STAT3, and YAP in CRC. Hundred and 13 CRC archival blocks were processed by TMA technique and immunostained with SIRT1, STAT3, and YAP antibodies. SIRT1, STAT3, and YAP are expressed in both tumor and stromal cells. SIRT1 expression in both the epithelial and stromal compartments was associated with favorable prognostic parameters, including longer overall and recurrence-free survival. In contrast, the epithelial and stromal expression of both STAT3 and YAP1 was associated with poor prognostic parameters, including short overall and recurrence-free survival. STAT3 and YAP epithelial expression showed a positive correlation with one another, but a negative correlation with epithelial SIRT1. While SIRT1 stromal expression was inversely correlated with stromal YAP expression, STAT3 and YAP concurrent stromal expression demonstrated a positive correlation with one another. There is crosstalk between CRC tumor and stromal cells by the coparallel expression of molecules such as SIRT1, STAT3, and YAP. There is a synergism between the STAT3 and YAP pathways in CRC at the level of the tumor and stroma. The tumor microenvironment of CRC could modulate tumor behavior by expressing markers suppressing invasion, such as SIRT1 or enhancing invasion, such as STAT3 and YAP.