BCAT1: A risk factor in multiple cancers based on a pan-cancer analysis

Abstract

Background: Although branched chain amino acid transaminase 1 (BCAT1) has been identified to play an essential role in multiple tumors, no studies on its role in pan-cancer have been consulted before.

Methods: The study comprehensively analyzes the expression, potential mechanisms, and clinical significance of BCAT1 in pan-cancer through utilizing 16,847 samples, providing novel clues for the treatment of cancers. A Kruskal-Wallis test and the Wilcoxon rank-sum and signed-rank tests were applied to investigate diverse BCAT1 expression between various groups (e.g., cancer tissues versus normal tissues). Spearman's rank correlation coefficient was used in all correlation analyses in the study. Cox analyses and Kaplan-Meier curves were utilized to identify the prognosis significance of BCAT1 expression in cancers. The significance of BCAT1 expression in differentiating cancer and non-cancer tissues was explored via the area under the receiver operating characteristic curves (AUC).

Results: The differential expression of BCAT1 was detected in various cancers (p < 0.05), which is relevant to some DNA methyltransferases expression. BCAT1 expression was associated with mismatch repair gene expression, immune checkpoint inhibitors expression, microsatellite instability, and tumor mutational burden in some cancers, indicating its potential in immunotherapy. BCAT1 expression showed prognosis significance and played a risk role in multiple cancers (hazard ratio > 0, p < 0.05). BCAT1 expression also demonstrated conspicuous ability to distinguish some cancers tissues from their normal tissues (AUC > 0.7), indicating its potential to detect cancers. Further analyses on head and neck squamous cell carcinoma certified upregulated BCAT1 expression at both mRNA and protein levels in this disease based on in-house tissue microarrays and multicenter datasets.

Conclusions: For the first time, the research comprehensively demonstrates the overexpression of BCAT1 in pan-cancer, which improves the understanding of the pathogenesis of BCAT1 in pan-cancer. Upregulated BCAT1 expression represented a poor prognosis for cancers patients, and it serves as a potential marker for cancer immunotherapy.

Keywords: cancer biology; cancer risk factors; immunology; prognosis; target therapy.