Dong Tianqi, Yuan Yuncang, Xiang Xudong, Sang Shuping, Shen Hao, Wang Lei, Yang Chunyan, Li Fangfang, Li Hongliang, Zheng Shangyong
School of Medicine, Yunnan University, Kunming, Yunnan, China.
Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
PeerJ. 2020 Nov 19;8:e10397. doi: 10.7717/peerj.10397. eCollection 2020.
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 CRC (colorectal cancer) remains controversial, and the association between the subcellular localization of YAP1 and clinical implications in CRC remains unknown.
In this study, we investigated the subcellular localization of YAP1 in CRC cells by immunohistochemistry and then associate these findings with clinical information in a large CRC cohort with 919 CRC patients.
The results show that CRC tissues has a significant higher expression of cytoplasmic YAP1 compared to adjacent normal tissues (all < 0.001). Cytoplasmic YAP1 expression was significantly associated with the number of lymph nodes removed and differentiation grade (all < 0.001). Furthermore, after correcting confounding variables, for example, TNM stage and differentiation grade, the multivariate Cox analysis confirmed cytoplasmic YAP1-high subgroup had a significant shorter DFS (HR = 3.255; 95% CI [2.290-4.627]; < 0.001) and DSS (HR = 4.049; 95% CI [2.400-6.830]; < 0.001) than cytoplasmic YAP1-low subgroup. High cytoplasmic YAP1 expression is associated with a worse survival in stage III CRC patients who received chemotherapy.
Cytoplasmic YAP1 could be could be utilized as a prognosis factor in CRC patients, and may be an indicator of whether certain patients population could benefit from postoperative chemotherapy.
Yes相关蛋白1（YAP1）是Hippo通路中最重要的效应分子之一，在多种癌症中发挥着至关重要的作用。然而，YAP1在结直肠癌（CRC）中是否为癌基因仍存在争议，且YAP1的亚细胞定位与CRC临床意义之间的关联尚不清楚。
在本研究中，我们通过免疫组织化学研究了YAP1在CRC细胞中的亚细胞定位，然后将这些发现与一个包含919例CRC患者的大型CRC队列的临床信息相关联。
结果显示，与相邻正常组织相比，CRC组织中细胞质YAP1的表达显著更高（均P<0.001）。细胞质YAP1表达与切除淋巴结数量和分化程度显著相关（均P<0.001）。此外，在校正混杂变量（如TNM分期和分化程度）后，多因素Cox分析证实，细胞质YAP1高表达亚组的无病生存期（DFS）显著短于细胞质YAP1低表达亚组（HR = 3.255；95%CI[2.290 - 4.627]；P<0.001），总生存期（DSS）也显著更短（HR = 4.049；95%CI[2.400 - 6.830]；P<0.001）。高细胞质YAP1表达与接受化疗的III期CRC患者的较差生存相关。
细胞质YAP1可作为CRC患者的预后因素，可能是某些患者群体是否能从术后化疗中获益的指标。
