Pan-cancer analysis to provide a reliable basis for the clinical use of TIM-3 immunosuppressants

Abstract

Abstract Background TIM-3 belongs to the immunoglobulin superfamily and is currently one of the most valuable immunosuppressants. HAVCR2 is the gene that codes for TIM-3, and its expression has been linked to the clinical efficacy of TIM-3 immunosuppressants. The study aims to provide potential guidance for the use of TIM-3 immunosuppressants in pan-cancer. Methods Data related to HAVCR2 in pan-cancer was obtained from multiple databases. First, differences in HAVCR2 expression between pan-cancerous and corresponding normal tissues were analyzed, and Survival rates were analyzed using Kaplan-Meier and Cox analyses. Besides,the correlation between HAVCR2 expression and DNA methyltransferases (DNMTs), tumor-infiltrating immune cells(TIICs), tumor mutational burden(TMB), microsatellite instability (MSI), mismatch repair (MMR), and immune checkpoint (ICP) was investigated by Spearman correlation analysis.Functional enrichment analysis of HAVCR2 was also performed to explore its biological and molecular roles in tumors. Finally, validation of HAVCR2 expression was performed in some cancer cell lines to analyze its differential expression. Results Our comprehensive pan-cancer analysis showed that HAVCR2 expression was significantly upregulated in most malignancies and correlated with poor prognosis. Secondly, there was a significant association between HAVCR2 methylation levels and survival prognosis in patients with multiple tumors, while patients with HAVCR2 mutated tumours showed a good prognosis. Moeeover, the expression of HAVCR2 was strongly associated with excessive infiltration of immune cells in the tumour microenvironment(TME). In addition, the expression of HAVCR2 significantly correlated with TMB, MSI, MMR, and ICP in different types of tumors, and the correlation results correlated with the efficacy of TIM-3 immunosuppressants in some cancer patients. More importantly,functional enrichment analysis based on HAVCR2 indicates that HAVCR2 acts primarily through the regulation of immunobiological processes in the TME.RT-PCR validated HAVCR2 expression in multiple cancer cell lines, consistent with the bioinformatic analysis results. Conclusions The expression of HAVCR2 is significantly correlated with heterogeneous features of pan-cancer, and the results of this correlation have potential value in guiding the clinical application of TIM-3 in pan-cancer spectrum.