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Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. The maximum number of deaths associated with kidney cancer can be attributed to ccRCC. Disruption of cellular proteostasis results in endoplasmic reticulum (ER) stress, which is associated with various aspects of cance...

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Autores principales: Zhang, Yuke, Song, Yancheng, Dai, Jiangwen, Wang, Zhaoxiang, Zeng, Yuhao, Chen, Feng, Zhang, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360548/
https://www.ncbi.nlm.nih.gov/pubmed/35959432
http://dx.doi.org/10.3389/fphar.2022.909123
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author Zhang, Yuke
Song, Yancheng
Dai, Jiangwen
Wang, Zhaoxiang
Zeng, Yuhao
Chen, Feng
Zhang, Peng
author_facet Zhang, Yuke
Song, Yancheng
Dai, Jiangwen
Wang, Zhaoxiang
Zeng, Yuhao
Chen, Feng
Zhang, Peng
author_sort Zhang, Yuke
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. The maximum number of deaths associated with kidney cancer can be attributed to ccRCC. Disruption of cellular proteostasis results in endoplasmic reticulum (ER) stress, which is associated with various aspects of cancer. It is noteworthy that the role of ER stress in the progression of ccRCC remains unclear. We classified 526 ccRCC samples identified from the TCGA database into the C1 and C2 subtypes by consensus clustering of the 295 ER stress-related genes. The ccRCC samples belonging to subtype C2 were in their advanced tumor stage and grade. These samples were characterized by poor prognosis and malignancy immune microenvironment. The upregulation of the inhibitory immune checkpoint gene expression and unique drug sensitivity were also observed. The differentially expressed genes between the two clusters were explored. An 11-gene ER stress-related prognostic risk model was constructed following the LASSO regression and Cox regression analyses. In addition, a nomogram was constructed by integrating the clinical parameters and risk scores. The calibration curves, ROC curves, and DCA curves helped validate the accuracy of the prediction when both the TCGA dataset and the external E-MTAB-1980 dataset were considered. Moreover, we analyzed the differentially expressed genes common to the E-MTAB-1980 and TCGA datasets to screen out new therapeutic compounds. In summary, our study can potentially help in the comprehensive understanding of ER stress in ccRCC and serve as a reference for future studies on novel prognostic biomarkers and treatments.
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spelling pubmed-93605482022-08-10 Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma Zhang, Yuke Song, Yancheng Dai, Jiangwen Wang, Zhaoxiang Zeng, Yuhao Chen, Feng Zhang, Peng Front Pharmacol Pharmacology Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. The maximum number of deaths associated with kidney cancer can be attributed to ccRCC. Disruption of cellular proteostasis results in endoplasmic reticulum (ER) stress, which is associated with various aspects of cancer. It is noteworthy that the role of ER stress in the progression of ccRCC remains unclear. We classified 526 ccRCC samples identified from the TCGA database into the C1 and C2 subtypes by consensus clustering of the 295 ER stress-related genes. The ccRCC samples belonging to subtype C2 were in their advanced tumor stage and grade. These samples were characterized by poor prognosis and malignancy immune microenvironment. The upregulation of the inhibitory immune checkpoint gene expression and unique drug sensitivity were also observed. The differentially expressed genes between the two clusters were explored. An 11-gene ER stress-related prognostic risk model was constructed following the LASSO regression and Cox regression analyses. In addition, a nomogram was constructed by integrating the clinical parameters and risk scores. The calibration curves, ROC curves, and DCA curves helped validate the accuracy of the prediction when both the TCGA dataset and the external E-MTAB-1980 dataset were considered. Moreover, we analyzed the differentially expressed genes common to the E-MTAB-1980 and TCGA datasets to screen out new therapeutic compounds. In summary, our study can potentially help in the comprehensive understanding of ER stress in ccRCC and serve as a reference for future studies on novel prognostic biomarkers and treatments. Frontiers Media S.A. 2022-07-26 /pmc/articles/PMC9360548/ /pubmed/35959432 http://dx.doi.org/10.3389/fphar.2022.909123 Text en Copyright © 2022 Zhang, Song, Dai, Wang, Zeng, Chen and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Yuke
Song, Yancheng
Dai, Jiangwen
Wang, Zhaoxiang
Zeng, Yuhao
Chen, Feng
Zhang, Peng
Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma
title Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma
title_full Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma
title_fullStr Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma
title_full_unstemmed Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma
title_short Endoplasmic Reticulum Stress-Related Signature Predicts Prognosis and Drug Response in Clear Cell Renal Cell Carcinoma
title_sort endoplasmic reticulum stress-related signature predicts prognosis and drug response in clear cell renal cell carcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360548/
https://www.ncbi.nlm.nih.gov/pubmed/35959432
http://dx.doi.org/10.3389/fphar.2022.909123
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