Pancancer Landscape of Long Non-coding RNA Expression and Immune Status of the Tumor Microenvironment in Japanese Cancer Patients.

Abstract

Background/aim: Advances in whole-genome sequencing have revealed that many RNA genes have important functions in various cellular processes and long non-coding RNAs (lncRNAs) have been attracting increasing attention. In the present study, we characterized a large number of lncRNAs from cancer patients and classified them based on their relationships with immune response-associated genes and cancer prognosis.

Materials and methods: 435 lncRNAs were identified as differentially expressed genes from 5,013 cancer patients using the limma package and were narrowed down to 80 lncRNAs commonly expressed in more than 4 cancer types. The relationships of these lncRNAs with immune response-associated genes were examined using Pearson's correlation and the tumor immune scoring system. Through a receiver operating characteristic (ROC) analysis of highly scored lncRNAs with the tumor-infiltrating lymphocyte (TIL) status using QuanTIseq, a cancer prognostic analysis was conducted using a multivariate Cox proportional hazards model.

Results: In a correlation analysis of 80 lncRNA genes and immune response-associated genes, lncRNA genes were scored and classified as high, intermediate, and low immune status score groups based on the Tumor Immune Status Scoring Algorithm (TIMMUSCORA). The ROC analysis of lncRNA genes with a high score (>200) revealed high sensitivity for the identification of TILs, such as CD8⁺ T cells and B cells. Furthermore, 11 of 80 lncRNA genes were identified as prognostic genes.

Conclusion: Twelve lncRNA genes with a high immune status score were identified as immunogenic and CD8⁺ T cell infiltration-associated genes, with two being indicators of a positive cancer prognosis. These results indicate the potential of 12 lncRNA genes with a high immune status score as immunogenic biomarkers associated with a positive immune response and prognosis.