The Study Of Prognostic Significance Of Cytoplasmic And Nuclear YAP1 Expression Level In Colorectal Cancer

Purpose:Yes associated protein 1(YAP1),which is a standout amongst the most essential effectors of the Hippo pathway,assumes a vital part in a few kinds of cancer.However,whether YAP1 is an oncogene in colorectal cancer(CRC)remains controversial,and the association between subcellular localization of YAP1 and clinical implications in CRC remains unknown.Method:In this study,we investigated subcellular localization of YAP1 in CRC cells by immunohistochemistry and then associate these findings with clinical information in a large cohort,including 922 CRC cases.Results:The results show that cytoplasmic YAP1 expression was significantly elevated in CRC tissues compared with the adjacent normal tissues(all P<0.001),interestingly,YAP1 NCR(Nuclear/Cytoplasmic Ratio)decrease progressively in adjacent normal tissues,adenomas,primary cancers,and metastatic CRC(all P<0.05).Cytoplasmic YAP1 expression was significantly associated with the number of resected lymph nodes and differentiation grade(all P<0.001),and YAP1 NCR had significant associations with TNM stage(P =0.02).Furthermore,after correcting confounding variables,TNM stage and differentiation grade,multivariate Cox analysis confirmed cytoplasmic YAP1-high subgroup had a significant shorter DFS(HR=3.255;95%CI=2.290-4.627;P<0.001)and DSS(HR=4.049;95%CI=2.400-6.830;P<0.001)than cytoplasmic YAP1-low subgroup,and YAP1 NCR-low subgroup had a significant shorter DFS(HR=2.295;95%CI=1.118-4.711;P=0.024)and DSS(HR=2.873;95%CI=1.045-7.902;P=0.041)than YAP1 NCR-high subgroup.In particular,adjuvant chemotherapy had differentially affected the survival of patients(stage II and III CRC)with different cytoplasmic YAP1 expression levels or different YAP1 NCR.Conclusion:Cytoplasmic YAP1 and YAP1 NCR could be utilized as a prognostic factor in CRC patients,and may be an indicator to adjudge whether certain patients’population could benefit from postoperative chemotherapy.