Expression analysis of BACH1 with clinical variables using the US breast cancer patient cohort

Studies on functional roles of BACH1 reveal that BACH1 promotes cancer metastasis and regulates metabolic networks for metastatic processes. However, little is known about BACH1 protein expression in breast tumors and its relevance to clinical variables as a biomarker for patients with breast tumors.

Using a tissue microarray (TMA) of breast tumor tissues isolated from a patient cohort (N = 130) expression of BACH1 and its target gene MCT1 (encoded by SLC16A1) were monitored by immunohistochemistry (IHC) assays and scored for further analyses. We examined the association between scores of BACH1 (Allredscoretotal) or MCT1 (Hscoretotal3×2×1x) with clinical variables including: breast cancer subtypes, tissue types, tumor size, patient's racial/ethnic background, and age group. Groups were compared using the Mann-Whitney U test (or the non-parametric Kruskal-Wallis test when appropriate) for numerical data. A proportional odds ordinal logistic model was used to examine multiple covariates. Associations between variables were evaluated with the Spearman's correlation coefficient.

BACH1 and MCT1 expression were detected in 90.76% (N = 118/130) and 92.30% (N = 120/130) of patients by IHC, respectively, in our study. After dichotomizing tumor size (small: 3-25 in diameter vs. big: 27-85 mm in diameter), BACH1 expression scores were significantly higher (p = 0.015) in the bigger tumor group (mean [SD]; 4.20 [1.796]) compared with the smaller tumor group (3.920 [1.693]). Of interest, we also observed significantly higher BACH1 scores (p = 0.004) in tumors from Black women (3.971 [1.514]; N = 69) compared with those of White women (3.02 [1.942]; N = 49). Consistent with mRNA expression analysis, BACH1 expression is most abundant in the basal-like tumors among all subtypes, specifically in Black women, whereas MCT1 expression scores are considerably higher in the basal-like tumors regardless of race. In addition, there was a positive association between BACH1 and MCT1 IHC scores in tumors from Black women, although a weak association between them in tumors from White women. In general, we did not detect associations between MCT1 IHC scores and race, tumor size, tissue types, or patient's age.

We found strong associations of BACH1 expression with tumor size and the basal-like subtype, respectively. Importantly, BACH1 expresses significantly higher in tumors from Black women than White women, as well as in the basal-like subtype of breast tumors from Black women. Our study suggests that BACH1 expression could serve as a potential race-associated biomarker indicating poor prognosis.