Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma
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 progn...
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PeerJ Inc.
2021-08-01
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| author | Na Li Jie Chen Qiang Liu Hongyi Qu Xiaoqing Yang Peng Gao Yao Wang Huayu Gao Hong Wang Zuohui Zhao |
| author_facet | Na Li Jie Chen Qiang Liu Hongyi Qu Xiaoqing Yang Peng Gao Yao Wang Huayu Gao Hong Wang Zuohui Zhao |
| author_sort | Na Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T06:35:23Z |
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| last_indexed | 2024-03-09T06:35:23Z |
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| spelling | doaj.art-a4805e0b34b74fe8bb76ac632b94c94f2023-12-03T11:00:02ZengPeerJ Inc.PeerJ2167-83592021-08-019e1190110.7717/peerj.11901Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinomaNa Li0Jie Chen1Qiang Liu2Hongyi Qu3Xiaoqing Yang4Peng Gao5Yao Wang6Huayu Gao7Hong Wang8Zuohui Zhao9Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment 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, Jinan, Shandong, ChinaDepartment of Pathology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment 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, Jinan, Shandong, ChinaDepartment of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, ChinaDepartment 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, Jinan, Shandong, ChinaMammalian 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.https://peerj.com/articles/11901.pdfMammalian target of rapamycinRenal cell carcinomaCancer-specific survivalTumor-infiltrating immune cellPrognosis |
| spellingShingle | Na Li Jie Chen Qiang Liu Hongyi Qu Xiaoqing Yang Peng Gao Yao Wang Huayu Gao Hong Wang Zuohui Zhao Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma PeerJ Mammalian target of rapamycin Renal cell carcinoma Cancer-specific survival Tumor-infiltrating immune cell Prognosis |
| title | Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma |
| title_full | Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma |
| title_fullStr | Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma |
| title_full_unstemmed | Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma |
| title_short | Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma |
| title_sort | prognostic significance and tumor immune infiltration of mtor in clear cell renal cell carcinoma |
| topic | Mammalian target of rapamycin Renal cell carcinoma Cancer-specific survival Tumor-infiltrating immune cell Prognosis |
| url | https://peerj.com/articles/11901.pdf |
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