Pan-cancer analysis: Predictive role of TAP1 in cancer prognosis and responses of immunotherapy

Abstract

Background: Transporter associated with antigen processing 1 (TAP1) is a transporter that processes and presents the major histocompatibility complex class I (MHC-I) restricted antigens, including tumor-associated antigens. TAP1 is aberrantly expressed in multiple cancer types, and also involves in tumor immunity. Therefore, the predictive role of TAP1 in cancer development and treatment is expected. Methods: Transcriptomic profiles were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Genetic alteration, protein distribution and interaction information were downloaded from cbioPortal, Human Protein Atlas (HPA) and Compartmentalized Protein-Protein Interaction (ComPPI), respectively. Single-cell analysis was conducted on Tumor Immune Single-cell Hub (TISCH) website. Gene set enrichment analysis (GSEA) was employed to investigate the functioning mechanism of TAP1 by R package “clusterProfiler”. Immune cell infiltration of Pan-cancer was explored by Tumor Immune Estimation Resource (TIMER) 2.0 webtool and visualized by R programming language. Correlation between TAP1 expression and immunotherapy biomarkers was explored using Spearman’s correlation test. Association with immunotherapy responses of TAP1 was investigated using the information of the cancer cohorts with patients received immune checkpoint inhibitors (ICIs). Results: TAP1 expression was elevated in most pan-cancer types and exhibited distinct prognostic value in diverse cancer types. Within tumor tissues, immune cells expressed more TAP1 than malignant cells. TAP1 expression was significantly correlated with immune-related pathways, infiltration of T lymphocytes and immunotherapeutic biomarkers. Cohort validation revealed a significant correlation with immune therapeutic effects and verified the prognostic role of TAP1 in immunotherapy. Western blot assay indicated that TAP1 is upregulated in GBMs compared with adjacent normal brain tissues (NBTs).Conclusion: TAP1 was a robust tumor biomarker, and a novel predictor of clinical prognosis and immunotherapeutic responses in distinct cancer types.

Pan-cancer analysis: predictive role of TAP1 in cancer prognosis and response to immunotherapy

“…Based on these data, we propose TAP1 as a novel biomarker for predicting patient prognosis and the effects of immunotherapy in diverse cancers. These results have been published as a preprint version [16], and our findings have potential to inform the future direction of research into TAP1.…”