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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

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

Author(s): 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* and Xiong-Lin Sun*

Volume 26, Issue 8, 2023

Published on: 31 October, 2022

Page: [1503 - 1518] Pages: 16

DOI: 10.2174/1386207325666220926123923

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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, long non-coding RNA, tumor mutation burden, prognostic model, tumor immune microenvironment, immune cells.

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