Sun Xujie, Zhang Jinyao, Dong Jiyan, Liu Li, Li Xue, Xing Puyuan, Ying Jianming, Che Yiqun, Li Junling, Yang Lin
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Transl Oncol. 2022 Nov;25:101538. doi: 10.1016/j.tranon.2022.101538. Epub 2022 Sep 11.
YAP1 (Yes-associated protein 1), an important effector of the Hippo pathway, acts as an oncogene and is overexpressed in various malignant tumors. However, the function and expression pattern of YAP1 in pulmonary large cell neuroendocrine carcinoma (LCNEC) have not been systematically established. This study aimed to explore the relationship between YAP1 expression and neuroendocrine differentiation markers and their prognostic significance in LCNEC.
YAP1 protein and neuroendocrine markers (INSM1, NeuroD1 and DLL3) expression were examined by immunohistochemical (IHC) staining in 80 resected pulmonary LCNEC cases. The possible association between these markers and clinicopathological features was evaluated and survival analyses were performed.
YAP1 was highly expressed in 25% LCNECs (20/80) , especially at a relatively higher T stage (p = 0.015). YAP1 expression was negatively correlated with INSM1 (χ=11.53, p = 0.001) and DLL3(χ=8.55, p = 0.004), but not with NeuroD1 (p = 0.482). For survival analyses, YAP1 expression was associated with worse disease-free survival (DFS) and overall survival (OS) (median DFS: 13 months vs. not reached (NR), p = 0.0096; median OS: not reached, NR vs. NR, p = 0.038), and was an unfavorable prognostic factor for DFS (HR:3.285; 95%CI: 1.526-7.071, p = 0.002) and OS (HR: 2.864, 95% CI: 0.932-8.796, p = 0.066).
YAP1 was found to be conversely correlated with neuroendocrine markers and a prognostic factor for worse survival in resected LCNEC patients, and mechanisms need to be further investigated.
YAP1（Yes相关蛋白1）是Hippo信号通路的重要效应分子，作为一种癌基因，在多种恶性肿瘤中过表达。然而，YAP1在肺大细胞神经内分泌癌（LCNEC）中的功能和表达模式尚未得到系统阐明。本研究旨在探讨YAP1表达与神经内分泌分化标志物之间的关系及其在LCNEC中的预后意义。
采用免疫组织化学（IHC）染色法检测80例手术切除的肺LCNEC病例中YAP1蛋白及神经内分泌标志物（INSM1、NeuroD1和DLL3）的表达。评估这些标志物与临床病理特征之间的可能关联，并进行生存分析。
25%的LCNEC（20/80）中YAP1高表达，尤其在相对较高的T分期中（p = 0.015）。YAP1表达与INSM1（χ=11.53，p = 0.001）和DLL3（χ=8.55，p = 0.004）呈负相关，但与NeuroD1无关（p = 0.482）。生存分析显示，YAP1表达与无病生存期（DFS）和总生存期（OS）较差相关（中位DFS：13个月对未达到（NR），p = 0.0096；中位OS：未达到，NR对NR，p = 0.038），并且是DFS（HR：3.285；95%CI：1.526 - 7.071，p = 0.002）和OS（HR：2.864，95%CI：0.932 - 8.796，p = 0.066）的不良预后因素。
发现YAP1与神经内分泌标志物呈负相关，是手术切除的LCNEC患者生存较差的预后因素，其机制有待进一步研究。
