Construction and Validation of T-cell Exhaustion-related Gene Signature for Predicting Prognosis in Diffuse Large B-cell Lymphoma.

Abstract

Background: T-cell exhaustion (TEX) is one reason for immunotherapy resistance among cancers, but the specific mechanism and influencing factors of TEX in diffuse large Bcell lymphoma (DLBCL) are not fully understood. This study aimed to establish a TEX signature for predicting the prognosis of DLBCL and investigate the immune characteristics related to the TEX signature.

Methods: The gene expression data of DLBCL were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Prognostic TEX related genes were selected by Cox regression analysis for prognostic signature (TEX score) construction. The correlation of risk grouping with immune cell infiltration was analyzed by CIBERSORT and ssGSEA. Molecular mechanisms between high and low TEX score groups were explored by gene set enrichment analysis (GSEA).

Results: A total of 115 differentially expressed TEX-related genes were selected, and 12 were prognosis-related after Cox regression. Following Ninesignature genes, including TRIM6, BIRC3, CTSC, GBP3, IRF3, TRIM22, IFI30, TRIM25 and BAG4 were identified to construct a TEX score. The receiver operator characteristic curve curves suggested that the model presented high predictive precision. A nomogram was established, which also had good prediction performance in survival prognosis. The composition of immune cells in the two risk groups was significantly different. GSEA identified 33 hallmarks between two risk groups, which were associated with immune cells infiltration and inflammation.

Conclusion: The TEX score has prognosis-predicting value for DLBCL and might be a valuable biomarker to guide clinical decision-making for patients with DLBCL.