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Cancer Cell International
Published in: Cancer Cell International 1/2021

01-12-2021 | Kidney Cancer | Primary research

The immune‐related biomarker TEK inhibits the development of clear cell renal cell carcinoma (ccRCC) by regulating AKT phosphorylation

Authors: Siming Chen, Mengxue Yu, Lingao Ju, Gang Wang, Kaiyu Qian, Yu Xiao, Xinghuan Wang

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

High immunogenicity is an important feature of ccRCC, but its underlying immune-related molecular mechanisms remain unclear. This study aimed to investigate the effect of immune-related gene TEK on ccRCC and its prognostic value.

Methods

The immune-related differentially expressed genes (DEGs) and transcription factors (TFs) in ccRCC were screened based on The Cancer Genome Atlas (TCGA) database, and a regulatory network of TF was constructed. Prognostic-related immune genes were screened by univariate Cox regression analysis and functional annotation was performed. Univariate and multivariate Cox regression analyses were performed to construct the immune gene risk model and identify the hub gene TEK that independently affected the prognosis of ccRCC. The effectiveness of the TEK was verified by external microarray datasets. The relationship between TEK and immune cells in ccRCC was evaluated based on Tumor Immune Estimation Resource (TIMER). The expression of TEK in clinical specimens was verified by qRT-PCR and immunohistochemical (IHC) staining. MTT and cloning formation assay were used to evaluate cell proliferation. Transwell assays were used to assess cell migration. Apoptosis was assessed by flow cytometry, and the expression of related proteins was detected by Western blot and immunofluorescence.

Results

We constructed a prognostic model consisting of 12 hub genes and performed risk scores to determine the relationship between these scores and prognosis. Through Cox regression analysis and survival analysis, TEK, an immune marker highly related to survival prognosis, was obtained and validated. In vitro experiments showed that knockdown of TEK promoted the proliferation and migration of ccRCC cells, and we found that TEK promoted apoptosis by regulating the phosphorylation of AKT, thereby inhibiting cell proliferation.

Conclusions

TEK plays an important role in risk assessment and survival prediction for ccRCC patients as a new immune gene and maybe an emerging target for immunotherapy for ccRCC patients.
Appendix
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Metadata
Title
The immune‐related biomarker TEK inhibits the development of clear cell renal cell carcinoma (ccRCC) by regulating AKT phosphorylation
Authors
Siming Chen
Mengxue Yu
Lingao Ju
Gang Wang
Kaiyu Qian
Yu Xiao
Xinghuan Wang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-01830-1

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