Carbonic anhydrase IX-related tumoral hypoxia predicts worse prognosis in breast cancer: A systematic review and meta-analysis

Abstract

BackgroundTumoral hypoxia is associated with aggressiveness in many cancers including breast cancer. However, measuring hypoxia is complicated. Carbonic anhydrase IX (CAIX) is a reliable endogenous marker of hypoxia under the control of the master regulator hypoxia-inducible factor-1α (HIF-1α). The expression of CAIX is associated with poor prognosis in many solid malignancies; however, its role in breast cancer remains controversial.MethodsThe present study performed a meta-analysis to evaluate the correlation between CAIX expression and disease-free survival (DFS) and overall survival (OS) in breast cancer.ResultsA total of 2,120 publications from EMBASE, PubMed, Cochrane, and Scopus were screened. Of these 2,120 publications, 272 full texts were reviewed, and 27 articles were included in the meta-analysis. High CAIX was significantly associated with poor DFS (HR = 1.70, 95% CI = 1.39–2.07, p < 0.00001) and OS (HR = 2.02, 95% CI 1.40–2.91, p = 0.0002) in patients with breast cancer. When stratified by subtype, the high CAIX group was clearly associated with shorter DFS (HR = 2.09, 95% CI =1.11–3.92, p = 0.02) and OS (HR = 2.50, 95% CI =1.53–4.07, p = 0.0002) in TNBC and shorter DFS in ER+ breast cancer (HR = 1.81 95% CI =1.38–2.36, p < 0.0001).ConclusionHigh CAIX expression is a negative prognostic marker of breast cancer regardless of the subtypes.