BTK is a Prognostic Biomarker for Multiple Human Tumors

Abstract

Bruton's tyrosine kinase (BTK), a key B-cell and macrophage kinase, plays a pivotal role in oncogenic pathways in many B-cell malignancies. BTK inhibitors have shown promising anti-tumor activity, first in B-cell malignancies and subsequently in other tumors. However, the prognostic role of BTK in human tumors remains largely unexplored. In this study, we aim to explore the prognostic value of BTK expression in 33 human tumors using pan-cancer analyses. Survival analyses, 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 correlation analysis was conducted to determine the interrelations between BTK and tumor mutational burden (TMB) and between BTK and microsatellite instability (MSI). The Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data (ESTIMATE) algorithm was used to explore the association of BTK with the tumor microenvironment and Gene Set Enrichment Analysis (GSEA) was used to examine the underlying mechanisms of BTK’s role in multiple tumors. BTK expression is closely associated with the prognosis of head and neck squamous cell carcinoma (HNSC), brain lower grade glioma (LGG), skin cutaneous melanoma (SKCM), and lung adenocarcinoma (LUAD). BTK expression was correlated with clinical stage, TMB, and MSI in 10 types of tumors. In HNSC, LGG, LUAD, and SKCM, BTK expression was positively correlated with immune and stromal scores. BTK is a prognostic biomarker in multiple tumors, especially in HNSC, LGG, LUAD, and SKCM, and this is closely associated with tumor microenvironment remodeling.