Investigation of the ABO gene as a biomarker in breast invasive carcinoma using cancer profiling and blood type distribution

Introduction Invasive breast carcinoma (BRCA) is one of the leading causes of cancer‑related mortality in women worldwide, highlighting the urgent need for novel prognostic biomarkers. The ABO gene has recently been implicated in various cancers. This study comprehensively investigated the expression pattern, clinical significance, and potential molecular mechanisms of ABO in BRCA. Method Multi‑omics data from The Cancer Genome Atlas and Genotype‑Tissue Expression databases were utilized. Human breast cancer tissue samples and matched adjacent normal tissue samples were obtained from patients who did not receive preoperative chemotherapy or radiotherapy at the First Affiliated Hospital of Zhengzhou University; non‑tumor specimens were also collected. We delineated the expression profile of the ABO gene in breast cancer tissues compared with normal breast tissues and across different molecular subtypes. We further evaluated its diagnostic utility and prognostic significance, and explored potential molecular mechanisms underlying ABO‑associated phenotypes as well as the distribution of ABO blood types. Quantitative reverse transcription polymerase chain reaction was performed on an independent clinical cohort (n=49 pairs) for validation. Results ABO expression was significantly downregulated in BRCA tissues compared with normal breast tissues. This low expression was associated with aggressive clinicopathological features, including human epidermal growth factor receptor 2‑positive status, estrogen receptor/progesterone receptor negativity, specific racial backgrounds, and basal‑like molecular subtypes. Functionally, ABO expression demonstrated substantial diagnostic value (area under the curve=0.812) and served as an independent prognostic factor for poor overall survival, disease‑specific survival, and progression‑free interval, although it showed limited predictive accuracy for 1‑, 3‑, and 5‑year survival rates. Mechanistically, gene set enrichment analysis linked low ABO expression to pathways involved in DNA replication and mitochondrial translation, and promoter hypermethylation may act as a potential regulatory mechanism underlying its downregulation. Reduced ABO expression in BRCA was validated in our independent clinical cohort. Discussion The ABO gene may serve as a novel diagnostic biomarker in BRCA. Its downregulation is potentially driven by epigenetic silencing and is linked to tumor proliferation and metabolism.