Bioinformatic Analysis Reveals Bone Marrow Kinase as a Potential Diagnostic and Prognostic Biomarker for Multiple Cancer Types.

Introduction: Bone marrow kinase, or BMX, is alternatively referred to as endothelial tyrosine kinase (Etk). It plays a vital role in the processes of cell proliferation, survival, immune activation, and the modulation of diverse signaling pathways. Since there are few direct comprehensive studies linking BMX role with multiple cancers, this study aimed to utilize bioinformatic tools to conduct a comprehensive analysis of BMX across multiple cancers, assessing its potential role.

Methods: Multiple databases including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), have been used to explore BMX expression across different cancers, which has been further validated by using Gene Expression Omnibus (GEO) public datasets. In addition, we used the Kaplan-Meier plotter to estimate overall survival and cBioPortal for genetic alterations analysis. This study accommodates several other analyses like clinical parameters, immune cell infiltration, and DNA promoter methylation profiles to evaluate the general role of BMX in several cancers.  Results: The present investigation revealed that the BMX gene expression was significantly downregulated and could serve as an effective diagnostic biomarker in five types of cancers, namely breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and rectum adenocarcinoma (READ) (all p < 0.05). Detailed analyses revealed notable downregulation of BMX in various clinical parameters such as age, gender, race, and cancer stage (all p < 0.05). To better understand the immunotherapeutic role of BMX, this investigation further examined the immune infiltration which exhibited positive correlations between BMX expression and the infiltration of immunological cells such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, especially in COAD, LUAD, and LUSC (all p < 0.05). In addition, the present study has demonstrated that diminished BMX gene expression is correlated with an unfavorable prognosis in kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), sarcoma (SARC), and uterine corpus endometrial carcinoma (UCEC); thus BMX gene expression can be used as a prognostic target for these specific cancers. Also, the results showed that the promoter methylation level of BMX was significantly elevated in LUAD and LUSC, whereas it was significantly decreased in BRCA (all p < 0.001). Importantly, our findings of significantly low BMX expression in LUAD and LUSC, along with their methylation profiles suggest that the low expression of BMX across these cancers is due to epigenetic factors. However, genetic alteration analysis revealed that mutations existed in only approximately 2% of the TCGA samples.

Conclusion: Our study revealed BMX as a diagnostic biomarker in BRCA, COAD, LUAD, LUSC, and READ and a prognostic biomarker in KIRC, LIHC, SARC, and UCEC. Furthermore, epigenetic variables may have a greater impact on BMX expression levels especially in LUAD and LUSC. This study also emphasized the role of BMX in the infiltration of immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, in certain cancers. The BMX expression level highlights the prognostic value and potential therapeutic potential of BMX.