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

Warapan Numprasit; Supaporn Yangngam; Jaturawitt Prasopsiri; Jean A Quinn; Joanne Edwards; Chanitra Thuwajit

doi:10.3389/fmed.2023.1087270

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

Front Med (Lausanne). 2023 Mar 17:10:1087270. doi: 10.3389/fmed.2023.1087270. eCollection 2023.

Authors

Warapan Numprasit^{1

2}, Supaporn Yangngam³, Jaturawitt Prasopsiri³, Jean A Quinn², Joanne Edwards², Chanitra Thuwajit³

Affiliations

¹ Division of Head Neck and Breast Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
² School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, United Kingdom.
³ Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Background: Tumoral 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.

Methods: The 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.

Results: A 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).

Conclusion: High CAIX expression is a negative prognostic marker of breast cancer regardless of the subtypes.

Keywords: breast cancer; carbonic anhydrase IX; meta-analysis; prognosis; survival.

Publication types

Systematic Review