Identification of a Somatic Mutation-Derived Long Non-Coding RNA Signatures of Genomic Instability in Renal Cell Carcinoma

Abstract

BackgroundRenal cell carcinoma (RCC) is a malignant tumor with high morbidity and mortality. It is characterized by a large number of somatic mutations and genomic instability. Long non-coding RNAs (lncRNAs) are widely involved in the expression of genomic instability in renal cell carcinoma. But no studies have identified the genome instability-related lncRNAs (GInLncRNAs) and their clinical significances in RCC.MethodsClinical data, gene expression data and mutation data of 943 RCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Based on the mutation data and lncRNA expression data, GInLncRNAs were screened out. Co-expression analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore their potential functions and related signaling pathways. A prognosis model was further constructed based on genome instability-related lncRNAs signature (GInLncSig). And the efficiency of the model was verified by receiver operating characteristic (ROC) curve. The relationships between the model and clinical information, prognosis, mutation number and gene expression were analyzed using correlation prognostic analysis. Finally, the prognostic model was verified in clinical stratification according to TCGA dataset.ResultsA total of 45 GInLncRNAs were screened out. Functional analysis showed that the functional genes of these GInLncRNAs were mainly enriched in chromosome and nucleoplasmic components, DNA binding in molecular function, transcription and complex anabolism in biological processes. Univariate and Multivariate Cox analyses further screened out 11 GInLncSig to construct a prognostic model (AL031123.1, AC114803.1, AC103563.7, AL031710.1, LINC00460, AC156455.1, AC015977.2, ‘PRDM16-dt’, AL139351.1, AL035661.1 and LINC01606), and the coefficient of each GInLncSig in the model was calculated. The area under the curve (AUC) value of the ROC curve was 0.770. Independent analysis of the model showed that the GInLncSig model was significantly correlated with the RCC patients’ overall survival. Furthermore, the GInLncSig model still had prognostic value in different subgroups of RCC patients.ConclusionOur study preliminarily explored the relationship between genomic instability, lncRNA and clinical characteristics of RCC patients, and constructed a GInLncSig model consisted of 11 GInLncSig to predict the prognosis of patients with RCC. At the same time, our study provided theoretical support for the exploration of the formation and development of RCC.

Development and Validation of Ferroptosis- and Immune-Related lncRNAs Signatures for Breast Infiltrating Duct and Lobular Carcinoma

“…found that the expression of AL035661.1 was downregulated and could serve as prognosis biomarkers of hepatocellular carcinoma ( 33 ). These results indicated that AL035661.1 was closely related to the development and progression of several cancers ( 32 , 33 ) and also increased the possibility of AL035661.1 as prognosis biomarker for BRCA patients with breast infiltrating duct and lobular carcinoma.…”

“…Fang et al. found that AL035661.1 was upregulated in renal cell carcinoma and positively associated with the poor prognosis ( 32 ). Similarly, we also found that the expression of AL035661.1 was decreased in patients with breast infiltrating duct and lobular carcinoma, and these patients with high expression of AL035661.1 exhibited worse OS.…”

Novel GIRlncRNA Signature for Predicting the Clinical Outcome and Therapeutic Response in NSCLC

“…LncRNAs play a critical role in maintaining genomic instability ( Nair et al, 2020 ; Jianfeng et al, 2021 ). Increasing evidence has revealed the prognostic significance of GIRlncRNAs for cancers ( Fang et al, 2021 ; Liang et al, 2021 ; Maimaiti et al, 2021 ; Yan et al, 2021 ). Since NSCLC possesses a poor survival prognosis due to limited diagnosis and treatment ( Zappa and Mousa, 2016 ; Li C. et al, 2019 ), we developed a prognostic GIRlncSig to support the clinical stratification and treatment decision for NSCLC patients.…”

Editorial: Long-non coding RNAs in renal cell carcinoma

“…In this current topic, an overview of lncRNAs in RCC is provided through 4 original research papers by 23 authors, and these studies expand our understanding of the important roles of lncRNAs in the progression of RCC (8)(9)(10)(11). Notably, Tan et al reported the overexpressed lncRNA DUXAP9 was associated with poorer overall survival and progression-free survival in clear cell RCC (ccRCC).…”

“…In this current topic, an overview of lncRNAs in RCC is provided through 4 original research papers by 23 authors, and these studies expand our understanding of the important roles of lncRNAs in the progression of RCC ( 8 – 11 ). Notably, Tan et al.…”