Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC). Despite the existing extensive research, the molecular and pathogenic mechanisms of ccRCC are elusive. We aimed to identify the immune-related lncRNA signature and molecular subtypes associated with ccRCC. By integrating 4 microarray datasets from Gene Expression Omnibus database, we identified 49 immune-related genes. The corresponding immune-related lncRNAs were further identified in the TCGA dataset. 12-lncRNAs prognostic and independent signature was identified through survival analysis and survival difference between risk groups was further identified based on the risk score. Besides, we identified 3 molecular subtypes and survival analysis result showed that cluster 2 has a better survival outcome. Further, ssGSEA enrichment analysis for the immune-associated gene sets revealed that cluster 1 corresponded to a high immune infiltration level. While cluster 2 and cluster 3 corresponded to low and medium immune infiltration level, respectively. In addition, we validated the 12-lncRNA prognostic signature and molecular subtypes in an external validation dataset from the ICGC database. In summary, we identified a 12-lncRNA prognostic signature which may provide new insights into the molecular mechanisms of ccRCC and the molecular subtypes provided a theoretical basis for personalized treatment by clinicians.

Highlights

  • Renal cell carcinoma (RCC) accounts for over 90% of all kidney cancer cases among human a­ dults[1]

  • We identified 12 long non-coding RNAs (lncRNAs) prognostic signature associated with Clear cell renal cell carcinoma (ccRCC) survival

  • Cumulative evidence reveals that dysregulated lncRNAs may serve as a critical biomarker for many types of cancers, in particular, esophageal squamous cell carcinoma and breast c­ ancer[18,19]

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Summary

Introduction

Renal cell carcinoma (RCC) accounts for over 90% of all kidney cancer cases among human a­ dults[1]. Despite interventions through chemotherapy and radiotherapy, ccRCC is prone to distant metastasis These metastases occur in lung, bone, liver, distant lymph nodes, and renal v­ ein[5]. A few effective biomarkers, in both early and advanced stages of ccRCC, have been identified. LncRNAs are non-coding RNAs composed of about 200 nucleotides in length. More specific and reliable lncRNA-based biomarkers need to be uncovered. This will thereby improve the prognostic accuracy of ccRCC. 3 molecular subtypes (cluster 1, cluster 2, and cluster 3) based on the immune lncRNA and gene expression profile were identified. The identification of immune-related lncRNA and molecular subtypes of ccRCC will advance the treatment of ccRCC patients, and provide a better understanding of the underlying molecular mechanisms of ccRCC

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