Li Na, Chen Jie, Liu Qiang, Qu Hongyi, Yang Xiaoqing, Gao Peng, Wang Yao, Gao Huayu, Wang Hong, Zhao Zuohui
Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
Department of Urology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
PeerJ. 2021 Aug 17;9:e11901. doi: 10.7717/peerj.11901. eCollection 2021.
Mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in cell proliferation, survival, metabolism and immunity, was reportedly activated in various cancers. However, the clinical role of mTOR in renal cell carcinoma (RCC) is controversial. Here we detected the expression and prognosis of total mTOR and phosphorylated mTOR (p-mTOR) in clear cell RCC (ccRCC) patients, and explored the interactions between mTOR and immune infiltrates in ccRCC. The protein level of mTOR and p-mTOR was determined by western blotting (WB), and their expression was evaluated in 145 ccRCC and 13 non-tumor specimens by immunohistochemistry (IHC). The relationship to immune infiltration of mTOR was further investigated using TIMER and TISIDB databases, respectively. WB demonstrated the ratio of p-mTOR to mTOR was higher in ccRCC than adjacent specimens ( = 3), and IHC analysis elucidated that p-mTOR expression was positively correlated with tumor size, stage and metastasis status, and negatively correlated with cancer-specific survival (CSS). In univariate analysis, high grade, large tumor, advanced stage, metastasis, and high p-mTOR expression were recognized as prognostic factors of poorer CSS, and multivariate survival analysis elucidated that tumor stage, p-mTOR and metastasis were of prognostic value for CSS in ccRCC patients. Further TIMER and TISIDB analyses uncovered that mTOR gene expression was significantly associated with numerous immune cells and immunoinhibitors in patients with ccRCC. Collectively, these findings revealed p-mTOR was identified as an independent predictor of poor survival, and mTOR was associated with tumor immune infiltrates in ccRCC patients, which validated mTOR could be implicated in the initiation and progression of ccRCC.
雷帕霉素哺乳动物靶点（mTOR）是一种参与细胞增殖、存活、代谢和免疫的丝氨酸/苏氨酸激酶，据报道在多种癌症中被激活。然而，mTOR在肾细胞癌（RCC）中的临床作用存在争议。在此，我们检测了透明细胞肾细胞癌（ccRCC）患者中总mTOR和磷酸化mTOR（p-mTOR）的表达及预后，并探讨了ccRCC中mTOR与免疫浸润之间的相互作用。通过蛋白质免疫印迹法（WB）测定mTOR和p-mTOR的蛋白水平，并通过免疫组织化学（IHC）在145例ccRCC和13例非肿瘤标本中评估它们的表达。分别使用TIMER和TISIDB数据库进一步研究mTOR与免疫浸润的关系。WB显示ccRCC中p-mTOR与mTOR的比值高于相邻标本（ = 3），IHC分析表明p-mTOR表达与肿瘤大小、分期和转移状态呈正相关，与癌症特异性生存（CSS）呈负相关。在单因素分析中，高分级、大肿瘤、晚期、转移和高p-mTOR表达被认为是CSS较差的预后因素，多因素生存分析表明肿瘤分期、p-mTOR和转移对ccRCC患者的CSS具有预后价值。进一步的TIMER和TISIDB分析发现，ccRCC患者中mTOR基因表达与多种免疫细胞和免疫抑制剂显著相关。总体而言，这些发现表明p-mTOR被确定为生存不良的独立预测因子，mTOR与ccRCC患者的肿瘤免疫浸润相关，这证实mTOR可能参与ccRCC的发生和发展。
