Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer. (20th April 2021)

• Record Type: Journal Article
• Authors: Alderdice, Matthew; Craig, Stephanie G; Humphries, Matthew P; Gilmore, Alan; Johnston, Nicole; Bingham, Victoria; Coyle, Vicky; Senevirathne, Seedevi; Longley, Daniel B; Loughrey, Maurice B; McQuaid, Stephen; James, Jacqueline A; Salto-Tellez, Manuel; Lawler, Mark; McArt, Darragh G
• Is Part Of: NAR genomics and bioinformatics. Volume 3:issue 2(2021)
• Publication Date: 2021-04-20
• Subjects: Genomics -- Periodicals; Bioinformatics -- Periodicals; 572.8
• DOI: 10.1093/nargab/lqab016
• Languages: English
• ISSNs: 2631-9268

Abstract

Abstract: Identifying robust predictive biomarkers to stratify colorectal cancer (CRC) patients based on their response to immune-checkpoint therapy is an area of unmet clinical need. Our evolutionary algorithm Atlas Correlation Explorer (ACE) represents a novel approach for mining The Cancer Genome Atlas (TCGA) data for clinically relevant associations. We deployed ACE to identify candidate predictive biomarkers of response to immune-checkpoint therapy in CRC. We interrogated the colon adenocarcinoma (COAD) gene expression data across nine immune-checkpoints ( PDL1, PDCD1, CTLA4, LAG3, TIM3, TIGIT, ICOS, IDO1 and BTLA ). IL2RB was identified as the most common gene associated with immune-checkpoint genes in CRC. Using human/murine single-cell RNA-seq data, we demonstrated that IL2RB was expressed predominantly in a subset of T-cells associated with increased immune-checkpoint expression ( P < 0.0001). Confirmatory IL2RB immunohistochemistry (IHC) analysis in a large MSI-H colon cancer tissue microarray (TMA; n = 115) revealed sensitive, specific staining of a subset of lymphocytes and a strong association with FOXP3+ lymphocytes ( P < 0.0001). IL2RB mRNA positively correlated with three previously-published gene signatures of response to immune-checkpoint therapy ( P < 0.0001). Our evolutionary algorithm has identified IL2RB to be extensively linked to immune-checkpoints in CRC; its expression should be investigated for clinical utility as a potential predictive biomarker for CRC patients receiving immune-checkpoint blockade.