Potential Role of AKR1B1 Gene Methylation in Diagnosis of Patients With Breast Cancer

Abstract

Background: In addition to the great challenge of early diagnosis and prognosis in breast cancer (BC), the role of gene promoters in BC remains largely unexplored. This study aimed to evaluate aldo-keto reductase family 1 member B1 ( AKR1B1) methylation as noninvasive biomarker for early BC diagnosis. Methods: A total of 200 (120 with BC, 40 with benign breast diseases, 40 healthy) Egyptian women were enrolled. AKR1B1 methylation level was determined using EpiTect Methyl II QPCR assay quantitative polymerase chain reaction. Results: Findings revealed that hypermethylation AKR1B1 was reported to be associated ( P < .0001) with BC cases (93.2 [75.4-98.6]) compared with benign (23.9 [22.6-48.3]) or healthy (15.5 [10.6-16]) controls. It had a great diagnostic power (area under the curve [AUC] = 0.909) that was superior to cancer antigen (CA) 15-3 (AUC = 0.681) and carcinoembryonic antigen (CEA) (AUC = 0.539). Interestingly, AKR1B1 hypermethylation was reported to be significant in identifying BC early stages (AUC = 0.899) and grades (AUC = 0.903). Independent to hormonal status and HER2neu expression, AKR1B1 hypermethylation was related to some tumor severity features, including advanced stages, high histological grades, and lymph node invasion. Also, AKR1B1 high degrees of methylation were significantly correlated with the increase in CEA ( r = .195; P = .027), CA-15.3 ( r = .351; P = .0001) and tumor stages ( r = .274; P = .014), grades ( r = .253; P = .024), and lymph node invasion ( r = .275; P = .014). Conclusions: This study revealed that aberrant AKR1B1 methylation could facilitate early BC detection from benign br0east disorders. Hypermethylated AKR1B1 was related to BC aggressiveness suggesting its potential role as diagnostic and prognostic BC biomarker.