Meng Mingming, Liu Sanhong, Wang Chen, Gu Xinjin, Linghu Enqiang, Xue Xinying
Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, P.R. China.
Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Oncol Lett. 2020 Dec;20(6):376. doi: 10.3892/ol.2020.12239. Epub 2020 Oct 21.
Pancreatic cancer is one of the most life-threatening malignancies worldwide. Despite advances in checkpoint immunotherapy for patients with cancer, the current immunotherapies have demonstrated limited benefits for the treatment of pancreatic cancer. Apart from the intricate microenvironments that restrict T-cell function, membrane proteins other than programmed death-ligand 1 may also facilitate immune escape of tumor cells. The present study investigated the membrane proteins of seven paired pancreatic adenocarcinoma (PAAD) and adjacent normal tissues with mass spectrometry, and identified 10 up-and eight downregulated membrane proteins in PAAD. Together with the online database analysis, the results showed that the CASK protein was upregulated in PAAD samples and cell lines, and predicts poor outcomes in patients with PAAD. Furthermore, the results exhibited downregulated CD36 and EPB42 in PAAD samples and cell lines, and higher levels of CD36. EPB42 was shown to predict improved survival outcomes in patients with PAAD. Overall, the results of the present study revealed PAAD-specific membrane proteins as potential diagnostic markers and drug-targets for the immunotherapy of pancreatic cancer.
胰腺癌是全球最具生命威胁的恶性肿瘤之一。尽管癌症患者的检查点免疫疗法取得了进展，但目前的免疫疗法对胰腺癌治疗的益处有限。除了限制T细胞功能的复杂微环境外，程序性死亡配体1以外的膜蛋白也可能促进肿瘤细胞的免疫逃逸。本研究通过质谱分析了7对胰腺腺癌（PAAD）及其相邻正常组织的膜蛋白，确定了PAAD中10种上调和8种下调的膜蛋白。结合在线数据库分析，结果显示CASK蛋白在PAAD样本和细胞系中上调，并预示PAAD患者预后不良。此外，结果显示PAAD样本和细胞系中CD36和EPB42下调，且CD36水平较高。EPB42被证明可预测PAAD患者的生存结果改善。总体而言，本研究结果揭示了PAAD特异性膜蛋白作为胰腺癌免疫治疗的潜在诊断标志物和药物靶点。
