Prognostic and tumor microenvironmental feature of clear cell renal cell carcinoma revealed by m6A and lactylation modification-related genes

Lin Yang; Xiaoyu Wang; Jiahao Liu; Xiaoqiang Liu; Sheng Li; Fuchun Zheng; Qianxi Dong; Songhui Xu; Jing Xiong; Bin Fu

doi:10.3389/fimmu.2023.1225023

Prognostic and tumor microenvironmental feature of clear cell renal cell carcinoma revealed by m6A and lactylation modification-related genes

Front Immunol. 2023 Aug 11:14:1225023. doi: 10.3389/fimmu.2023.1225023. eCollection 2023.

Authors

Lin Yang¹, Xiaoyu Wang¹, Jiahao Liu¹, Xiaoqiang Liu¹, Sheng Li¹, Fuchun Zheng¹, Qianxi Dong¹, Songhui Xu¹, Jing Xiong¹, Bin Fu¹

Affiliation

¹ Department of Urology, First Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

Background: Both lactylation and m6A modification have important implications for the development of clear cell renal cell carcinoma (ccRCC), and we aimed to use crosstalk genes of both to reveal the prognostic and immunological features of ccRCC.

Methods: Our first step was to look for lactylation-related genes that differed between normal and tumor tissues, and then by correlation analysis, we found the genes associated with M6A. Following that, ccRCC subtypes will be identified and risk models will be constructed to compare the prognosis and tumor microenvironment among different subgroups. A nomogram was constructed to predict the prognosis of ccRCC, and in vitro, experiments were conducted to validate the expression and function of key genes.

Results: We screened 100 crosstalk genes and identified 2 ccRCC subtypes. A total of 11 prognostic genes were screened for building a risk model. we observed higher immune scores, elevated tumor mutational burden, and microsatellite instability scores in the high-risk group. Therefore, individuals classified as high-risk would derive greater benefits from immunotherapy. The nomogram's ability to predict overall survival with a 1-year AUC of 0.863 demonstrates its significant practical utility. In addition, HIBCH was identified as a potential therapeutic target and its expression and function were verified by in vitro experiments.

Conclusion: In addition to developing a precise prognostic nomogram for patients with ccRCC, our study also discovered the potential of HIBCH as a biomarker for the disease.

Keywords: M6A; clear cell renal cell carcinoma; immunotherapy; lactylation; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma*
Carcinoma, Renal Cell* / diagnosis
Carcinoma, Renal Cell* / genetics
Humans
Kidney Neoplasms* / diagnosis
Kidney Neoplasms* / genetics
Prognosis
Tumor Microenvironment / genetics

Grants and funding

This study was supported by the Jiangxi Provincial “Double Thousand Plan” Fund Project (jxsq2019201027), Key Project of Natural Science Foundation of Jiangxi Province (20212ACB206013), and Natural Science Foundation of Jiangxi, China (20212BAB206038), the Jiangxi Provincial Department of Health Project (202210339) to JX, and the National Natural Science Foundation of China (82172921) to SX.