Background: Long non-coding RNAs (lncRNAs) are now under discussion as novel promising
biomarkers for
clear cell renal cell carcinoma (ccRCC). However, the role of
genomic instability-associated
lncRNA signatures in
tumors has not been thoroughly uncovered. The purpose of our study is to probe the role of
genomic instability-derived
lncRNA signature (GILncSig) and to further investigate the mechanism of
genomic instability-mediated ccRCC progression. Methods: The transcriptome data and somatic mutation profiles of ccRCC as well as clinical characteristics used in this study were obtained from The
Cancer Genome Atlas database and Gene Expression Omnibus database. Lasso regression analysis was performed to construct the GILncSig. Gene set enrichment analysis (GSEA) was performed to elucidate the biological functions and relative pathways. CIBERSORT and EPIC algorithm were applied to calculate the proportion of immune cells in ccRCC. ESTIMATE algorithm was utilized to compute the immune microenvironment scores. Results: In total, 148 novel
genomic instability-derived lncRNAs in ccRCC were identified. Immediately, on the basis of univariate cox analysis and lasso analysis, a GILncSig was appraised, through which the patients were allocated into High-Risk and Low-Risk groups with significantly different characteristics and prognoses. In addition, we confirmed that the somatic mutation count,
tumor mutation burden, and the expression of UBQLN4, which were ascertainably associated with
genomic instability, were significantly correlated with the GILncSig, indicating its reliability as a measurement of the
genomic instability. Furthermore, the efficiency of GILncSig in prognostic aspects was better than the single mutation gene in ccRCC. In addition, MNX1-AS1 was defined to be a potential
biomarker characterized by strong correlation with clinical features. Moreover, GSEA results indicated that the
IL6/JAK/STAT3/SIGNALING pathway could be considered as a potential mechanism of
genomic instability to influence
tumor progression. Besides, the immune microenvironment showed significant differences between the GS-like group and the GU-like group, which was specifically manifested as high expression of CTLA4, GITR, TNFSF14, and regulatory T cells (Tregs) as well as low expression of endothelial cells (ECs) in the GU-like group. Finally, the prognostic value and clinical relevance of GILncSig were verified in GEO datasets and other urinary
tumors in TCGA dataset. Conclusion: In conclusion, our study provided a new perspective for the role of lncRNAs in
genomic instability and revealed that
genomic instability may mediate
tumor progression by affecting immunity. Besides, MNX1-AS1 played critical roles in promoting the progression of ccRCC, which may be a potential therapeutic target. What is more, the immune atlas of
genomic instability was characterized by high expression of CTLA4, GITR, TNFSF14, and Tregs, and low expression of ECs.