Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma

PeerJ

article

Na Li¹  Jie Chen¹  Qiang Liu³  Hongyi Qu⁴  Xiaoqing Yang⁵  Peng Gao³  Yao Wang³  Huayu Gao⁴  Hong Wang¹  Zuohui Zhao⁴ 

[1] Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital;Department of Urology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University;Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital;Department of Pediatric Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development;Department of Pathology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital

关键词: Mammalian target of rapamycin;    Renal cell carcinoma;    Cancer-specific survival;    Tumor-infiltrating immune cell;    Prognosis;   

DOI  :  10.7717/peerj.11901

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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 (n = 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.

【 授权许可】

CC BY