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.

The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects

“…In conclusion, BCAT may be a target for the treatment and prognosis of various diseases, such as LC, BC, AD, IR, etc., which indicates that BCAT gene-targeted therapy will be a promising strategy. In addition, the changes in BCAT1 levels are statistically different in different tumors, and its overexpression in pan-cancer has very obvious prognostic significance (102). There are no clear results so far on the abnormal expression of BCAT in different cancers, and the results found by different researchers are contradictory, which needs to be further studied in the future.…”

Analysis of immunotherapeutic response-related signatures in esophageal squamous-cell carcinoma

“…STRA6 , IGFL2 , USP2 and CASP14 are associated with the prognosis of other cancers, including hepatocellular carcinoma, bladder cancer, gastric cancer and clear cell renal cell carcinoma ( 42 – 48 ).The overexpression of CFTR suppressed the proliferation and migration/invasion of ESCC cells and was associated with a good patient prognosis ( 49 ). SERPINH1 and BCART1 are associated with various immune checkpoint genes in some cancers ( 41 , 50 , 51 ). The absence of NK cell-heparanase impaired the effect of immune checkpoint blockade immunotherapy ( 39 ).…”

The emerging role of the branched chain aminotransferases, BCATc and BCATm, for anti-tumor T-cell immunity

“…Some published data and ongoing research suggest that the BCAT isoenzymes may exert immunosuppressive functions in the TME [ 12 – 14 , 48 , 54 , 70 ] . As described in Ananieva’s reports, the BCAT isoenzymes might be a part of a critical resistance mechanism that involves a BCAT-dependent negative feedback regulation of mTORC1 signaling during T-cell activation and may serve as an essential metabolic checkpoint of T-cell function in TME [ 48 , 54 ] .…”

“…The cytosolic and mitochondrial branched chain amino transferases, BCATc and BCATm, otherwise referred to by gene names BCAT1 and BCAT2 , respectively, are responsible for the first step in the degradation of the branched chain amino acids (BCAAs), leucine, isoleucine, and valine. These proteins have only recently emerged as candidates with immunosuppressive properties [ 12 – 14 ] . BCAAs are required for survival of both cancer and immune cells; they are a well-established source of fuel and by-products of their degradation are used to support the increased biosynthetic demands of proliferating cells [ 15 ] .…”