Prognostic And Immunological Implications of BTK Expression In Pan-Cancer

Abstract Background: Cancer poses a serious threat to human health. Clarifying the potential significance of Bruton's tyrosine kinase (BTK)in cancer has potential clinical value. This study examined the prognostic and immunological value of BTK gene expression in pan-cancer.Methods: We evaluated the gene expression of BTK in tumor tissues and normal tissues in different cancers. Survival analysis, including Kaplan–Meier analysis and Cox analysis, were performed to explore the prognostic value of BTK for pan-cancer based on survival data from The Cancer Genome Atlas (TCGA) database. Spearman’s method was conducted to analyze the interrelation between BTK gene expression and tumor mutational burden (TMB)and microsatellite instability (MSI). We explored the association of BTK expression with the tumor microenvironment based on Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Co-expression analysis of BTK expression and immune-related genes was performed. We used Gene Set Enrichment Analysis (GSEA) to examine the molecular mechanisms and pathways of BTK in pan-cancer.Results: High BTK expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) was positively correlated with patient prognosis, while high expression of BTK in lymphoid neoplasm diffuse large B cell lymphoma (DLBC), brain lower grade glioma (LGG) and esophageal carcinoma (ESCA) corresponded with a worse prognosis. Cox analysis showed that BTK was closely associated to the prognosis of HNSC, LGG, SKCM and LUAD. BTK expression was correlated with clinical stage, TMB and MSI of 10 types of tumors. In HNSC, LGG, LUAD and SKCM, the expression of BTK was positive correlated with immune and stromal scores. Conclusion: BTK expression can act as a prognostic factor in various cancers, especially in HNSC, LGG, LUAD and SKCM, and this may be from its close association with TMB, MSI and immune cell infiltration.