A pan-cancer analysis of the biological function and clinical value of BTLA in tumors

Abstract

B and T-lymphocyte attenuator (BTLA) plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases, especially cancer immunity. However, the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed. This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression, its clinical value, immune infiltration, and the correlation with immune-related genes in various cancers. Data regarding mRNA expression, miRNA expression, lncRNA expression, and clinical data of patients of 33 existing cancers were collected from the TCGA database. Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database. Based on bioinformatics analysis methods, the relationship between various types of cancers and BTLA was thoroughly investigated, and a competing endogenous RNA network of BTLA, target miRNA, and interacting lncRNA was constructed. The Kaplan-Meier (KM) prognostic analysis of BTLA and target miRNA (has-miR-137) in various types of cancers was completed using the KM plotter. BTLA expression varied in different cancers, with statistical significance in nine cancer types. KM plotter to analyze the overall survival (OS) and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers; the OS of 8 type of cancers was also statistically different.Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene (CTLA4 and PDCD1) expression. Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways, including immune response regulation, cell surface receptor signaling pathway, antigen binding, antigen receptor-mediated signaling pathway, and leukocyte migration. BTLA has the potential as a prognostic marker for CLL, COAD, NSCLC, and OV and a diagnostic marker for CLL, COAD, and KIRC. BTLA has a close and complex relationship with the occurrence and development of tumors, and cancer immunotherapy for BTLA is worthy of further analysis.

BTLA biology in cancer: from bench discoveries to clinical potentials

“…Consistent with the results presented above, in a recent study by Ijang et al, the authors analyzed mRNA expression of BTLA in 33 different cancers using the TGAA database, as well as the prognostic value of BTLA on OS. Those findings confirmed the diverse consequences of BTLA expression in different cancers [ 98 ]. To summarize, the studies described above have been presented in Table 1 .…”

Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation

“…BTLA is expressed on both CD4 + and CD8 + T cells and the expression levels are related to T cell stage of differentiation and activation processes, with the expression transiently increased upon activation, but decreased in activated T cells ( 61 ). In NK cells BTLA induces immunosuppression ( 62 ), mainly by inhibiting NK cell-mediated cytotoxicity ( 63 ).…”

The role of Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in promoting human tumors: Literature review and pan-cancer analysis

“…The rising incidence and mortality of tumors have become a burden all over the world, so looking for markers with broad cancer-promoting effects is still necessary [ [1] , [2] , [3] , [4] , [5] ]. Cyclin dependent kinase inhibitor 3 ( CDKN3 ), is a cell cycle regulator [ 6 ].…”