Construction of an endoplasmic reticulum stress-related gene model for predicting prognosis and immune features in kidney renal clear cell carcinoma

Yuanhao Shen; Yinghao Cao; Lei Zhou; Jianfeng Wu; Min Mao

doi:10.3389/fmolb.2022.928006

Construction of an endoplasmic reticulum stress-related gene model for predicting prognosis and immune features in kidney renal clear cell carcinoma

Front Mol Biosci. 2022 Sep 2:9:928006. doi: 10.3389/fmolb.2022.928006. eCollection 2022.

Authors

Yuanhao Shen¹, Yinghao Cao², Lei Zhou², Jianfeng Wu², Min Mao²

Affiliations

¹ Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: Kidney renal clear cell carcinoma (KIRC) is one of the most lethal malignant tumors with a propensity for poor prognosis and difficult treatment. Endoplasmic reticulum (ER) stress served as a pivotal role in the progression of the tumor. However, the implications of ER stress on the clinical outcome and immune features of KIRC patients still need elucidation. Methods: We identified differentially expressed ER stress-related genes between KIRC specimens and normal specimens with TCGA dataset. Then, we explored the biological function and genetic mutation of ER stress-related differentially expressed genes (DEGs) by multiple bioinformatics analysis. Subsequently, LASSO analysis and univariate Cox regression analysis were applied to construct a novel prognostic model based on ER stress-related DEGs. Next, we confirmed the predictive performance of this model with the GEO dataset and explored the potential biological functions by functional enrichment analysis. Finally, KIRC patients stratified by the prognostic model were assessed for tumor microenvironment (TME), immune infiltration, and immune checkpoints through single-sample Gene Set Enrichment Analysis (ssGSEA) and ESTIMATE analysis. Results: We constructed a novel prognostic model, including eight ER stress-related DEGs, which could stratify two risk groups in KIRC. The prognostic model and a model-based nomogram could accurately predict the prognosis of KIRC patients. Functional enrichment analysis indicated several biological functions related to the progression of KIRC. The high-risk group showed higher levels of tumor infiltration by immune cells and higher immune scores. Conclusion: In this study, we constructed a novel prognostic model based on eight ER stress-related genes for KIRC patients, which would help predict the prognosis of KIRC and provide a new orientation to further research studies on personalized immunotherapy in KIRC.

Keywords: endoplasmic reticulum stress; immunotherapy; kidney renal clear cell carcinoma; prognosis; tumor microenvironment.