Effect of COL4A1 Expression on the Survival of Neoadjuvant Chemotherapy Breast Cancer Patients

Optimal therapy for each patient depends on their subtype, anatomic cancer stage, gene status, and preferences. Neoadjuvant chemotherapy-treated tumors have shown attenuated tumor growth, but the therapy cannot completely reduce tumor cell dissemination to blood stream and distant metastasis. Though it has been indicated that the protein of the collagen type IV alpha 1 (COL4A1) gene is induced by p53 to inhibit angiogenesis and tumorigenic activity in cancer cells, its prognostic significance in breast cancer (BC) patients has not yet been fully elucidated. We analysed 206 BC and fresh paired-match adjacent normal breast tissue from tissue microarrays (TMAs) and COL4A1-stained TMAs using immunohistochemistry. These were used to evaluate COL4A1 expression in BC and to analyse the relationship between this expression and clinicopathological factors and prognosis. The expression of the COL4A1 protein was significantly higher in normal adjacent tissue than in the tumor tissues of BC (P<0.0001). The low COL4A1 expression of the BC patients had decreased metastasis incidence ratio than those exhibiting high COL4A1 expression (P=0.034). Low COL4A1 expression in the tumor cells of BC patients was found to significantly reduce the overall survival (OS) and relapse-free survival (RFS) rates of neoadjuvant chemotherapy patients (P=0.047 and P=0.025, respectively). We also validated the results to ensure their consistency with a web server program for survival analysis from the Cancer Genome Atlas (TCGA) database (P=0.057). Additionally, COL4A1 expression was positively correlated with p53 expression (P=0.00076). Thus, we present clinical evidence that COL4A1 expression can be used as a biomarker of better prognosis of BC patients receiving neoadjuvant chemotherapy.