Dr. Jiyoung LeeGeorge Washington University, USA
Title: Potential biomarker of BACH1 with clinical variables in breast cancer patients
Background: Functional studies of BACH1 indicate that BACH1 promotes cancer metastasis and regulates metabolic networks for metastatic processes. In addition, expression analysis of BACH1 mRNA and its target gene signature using the Cancer Genome Atlas (TCGA) patient cohort showed poor prognosis of breast cancer patients. However, little is known about protein expression of BACH1 in breast tumors as a biomarker and its relevance to breast cancer risk factors.
Methods: Using a tissue microarray (TMA) of breast tumor tissues isolated from a patient cohort (n = 124), BACH1 and its target MCT1 (encoded by SLC16A1) were stained by immunohistochemistry (IHC) assays and scored for further analyses. We examined the association between scores of BACH1 (Allredscoretotal) or MCT1 staining (Hscoretotal3x2x1x) with clinical variables including: subtypes (luminal A/B, basal-like, HER2-positive), tissue types (ductal carcinoma in situ, hyperplasia, lymph node metastasis, tumors), tumor size (diameter), race (Black or white), age (below 55 or 55 and older), and life styles risk factors (marital status and alcohol history). These associations were analyzed using nonparametric approaches such as the Mann-Whitney U test or the Spearman’s rank correlation coefficient.
Results: BACH1 and MCT1 expression was detected in 90.76 % (N = 118/130) and 92.30 % (N = 120/130) of total patients by IHC, respectively. 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 (4.200 ± 1.796, mean ± SD) compared with the smaller tumor group (3.920 ± 1.693). Of interest, we also observed markedly higher BACH1 scores in tumors from Black women (3.971 ± 1.514, mean ± SD, N = 69) compared with those of White women (3.02 ± 1.942, N = 49) (p = 0.014). Remarkably, BACH1 expression by IHC is more abundant in basal-like tumors than tumors of other subtypes specifically in Black women, not in White women, whereas MCT1 expression scores are considerably higher in basal-like tumors regardless of race. In addition, there was a positive association between BACH1 and MCT1 IHC scores in Black women, although no association between BACH1 and MCT1 scores was found in White patients. In general, there was a near-null association between MCT1 IHC scores and race, tumor size, tissue types, patient’s age, alcohol history, or marital status.
Conclusions: We observed strong association of BACH1 expression with clinical variables such as tumor size and basal-like breast tumor type. Importantly, BACH1 expression is higher in Black women than in white women, as well as in basal-like subtypes of breast tumors from Black women. BACH1 expression might be a potential race-associated biomarker indicating poor prognosis for breast cancer patients.
To be updated