A Novel Tumor Mutation Burden Related lncRNA Signature Identified Prognosis and Tumor Immune Microenvironment Features in Clear Cell Renal Cell Carcinoma

Lin Lin; Xiao-Hui Wu; Jun-Ming Zhu; Shao-Hao Chen; Ye-Hui Chen; Fei Lin; Xue-Yi Xue; Yong Wei; Ning Xu; Qing-Shui Zheng; Xiong-Lin Sun

doi:10.2174/1386207325666220926123923

A Novel Tumor Mutation Burden Related lncRNA Signature Identified Prognosis and Tumor Immune Microenvironment Features in Clear Cell Renal Cell Carcinoma

Comb Chem High Throughput Screen. 2023;26(8):1503-1518. doi: 10.2174/1386207325666220926123923.

Authors

Lin Lin¹, Xiao-Hui Wu², Jun-Ming Zhu², Shao-Hao Chen², Ye-Hui Chen², Fei Lin², Xue-Yi Xue^{2

3}, Yong Wei², Ning Xu^{2

3}, Qing-Shui Zheng², Xiong-Lin Sun²

Affiliations

¹ Department of Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
² Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
³ Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.

Abstract

Background: Emerging evidence indicates that long noncoding RNA (lncRNA) plays an important biological role in clear cell renal cell carcinoma (ccRCC); however, the clinical value of tumor mutation burden-related lncRNA in ccRCC patients is unknown yet.

Methods: Somatic mutation profiles and lncRNA expression data of ccRCC were downloaded from the TCGA database. We retrospectively analyzed lncRNA expression data and survival information from 116 patients with ccRCC fromJanuary 2013 to January 2014. Univariate and multivariate Cox regression analyses were performed to construct lncRNA signature, and the prognosis value was determined by Kaplan-Mayer and receiver operating characteristic curve (ROC) analysis.

Results: Based on 160 differentially expressed TMB-related lncRNAs, two TMB-related molecular clusters with distinct immune checkpoints expression and immune cells infiltration were established for ccRCC patients. Moreover, a novel TMB-related lncRNA signature was constructed based on five lncRNAs for individualized prognosis assessment. High-risk group represents significantly worse overall survival in all cohorts. The area under the ROC curve was 0.716, 0.775 and 0.744 in the training cohort, testing cohort and TCGA cohort, respectively. Results of qRT-PCR successfully validated the expression levels of AP002360.3, LINC00460, AL590094.1, LINC00944 and LINC01843 in HK-2, 786-O, 769-P and ACHN cells. More importantly, the predictive performance of TMB-related lncRNA signature was successfully validated in an independent cohort of 116 ccRCC patients at our institution.

Conclusion: This study successfully developed and validated a novel TMB-related lncRNA signature for individualized prognosis assessment of ccRCC patients.

Keywords: Clear cell renal cell carcinoma; immune cells; long non-coding RNA; prognostic model; tumor immune microenvironment; tumor mutation burden.

Publication types

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

MeSH terms

Carcinoma, Renal Cell* / diagnosis
Carcinoma, Renal Cell* / genetics
Humans
Kidney Neoplasms* / diagnosis
Kidney Neoplasms* / genetics
Mutation
RNA, Long Noncoding* / genetics
Retrospective Studies
Tumor Microenvironment / genetics

Substances

RNA, Long Noncoding