High cytoplasmic YAP1 expression predicts a poor prognosis in patients with colorectal cancer.
High cytoplasmic YAP1 expression predicts a poor prognosis in patients with colorectal cancer.
复制标题
细胞质 YAP1 高表达预示结直肠癌患者预后不良
作者：
Dong T;Yuan Y;Xiang X;Sang S;Shen H;Wang L;Yang C;Li F;Li H;Zheng S
是相关蛋白1（YAP 1）是Hippo通路中最重要的效应子之一，在几种癌症中发挥着重要作用。然而，YAP 1是否是CRC（结直肠癌）中的癌基因仍然存在争议，并且YAP 1的亚细胞定位与CRC的临床意义之间的关联仍然未知。在这项研究中，我们通过免疫组化研究了结直肠癌细胞中YAP 1的亚细胞定位，然后将这些发现与919例结直肠癌患者的大型结直肠癌队列的临床信息相关联。结果显示，大肠癌组织胞浆YAP 1的表达显著高于癌旁正常组织（P均< 0.001）。胞浆YAP 1表达与淋巴结切除数、分化程度有关（P均< 0.001）。在校正混杂变量（如TNM分期和分化程度）后，多变量考克斯分析证实胞浆YAP 1高表达亚组的DFS显著缩短（HR = 3.255; 95%CI [2.290-4.627]; P < 0.001）和DSS（HR = 4.049; 95%CI [2.400-6.830]; P < 0.001）。高细胞质YAP 1表达与接受化疗的III期CRC患者的生存率较差相关。胞浆YAP 1可作为结直肠癌患者的预后指标，并可作为某些患者群体是否能从术后化疗中获益的指标。
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 P < 0.001). Cytoplasmic YAP1 expression was significantly associated with the number of lymph nodes removed and differentiation grade (all P < 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]; P < 0.001) and DSS (HR = 4.049; 95% CI [2.400–6.830]; P < 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.