NDLI: Hypoxia-regulated carbonic anhydrase IX (CAIX) protein is an independent prognostic indicator in triple negative breast cancer

Content Provider	Springer Nature : BioMed Central
Author	Ong, Chong Hui Clara Lee, Dong Yeul Lee, Bernett Li, Huihua Lim, Jeffrey Chun Tatt Lim, Johnathan Xiande Yeong, Joe Poh Sheng Lau, Hiu Yeung Thike, Aye Aye Tan, Puay Hoon Iqbal, Jabed
Abstract	Background The effect of extracellular microenvironment (hypoxia and pH) has been regarded as a key hallmark in cancer progression. The study aims to investigate the effects of carbonic anhydrase IX (CAIX), a key hypoxia-inducible marker, in triple-negative breast cancer (TNBC) in correlation with clinicopathological parameters and predicting survival outcomes. Methods A total of 323 TNBC cases diagnosed at the Department of Anatomical Pathology, Singapore General Hospital from 2003 to 2013 were used. Immunohistochemical staining (IHC) was performed using CAIX antibody and digital mRNA quantification was performed using NanoString assays. CAIX membranous expression was correlated with clinicopathological parameters using Chi-squared test or Fisher’s exact tests. Disease-free survival (DFS) and overall-survival (OS) were estimated using Kaplan–Meier analysis and compared between groups with the log-rank test. Results Forty percent of TNBCs were observed to express CAIX protein and demonstrated significant association with larger tumour size (P = 0.002), higher histological grade (P < 0.001), and significantly worse disease-free survival (DFS) and overall survival (OS) (after adjustment: HR = 2.99, 95% CI = 1.78–5.02, P < 0.001 and HR = 2.56, 95% CI = 1.41–4.65, P = 0.002, respectively). Gene ontology enrichment analysis revealed six significantly enriched cellular functions (secretion, cellular component disassembly, regulation of protein complex assembly, glycolytic process, cellular macromolecular complex assembly, positive regulation of cellular component biogenesis) associated with genes differentially expressed (CAIX, SETX, WAS, HK2, DDIT4, TUBA4α, ARL1). Three genes (WAS, SETX and DDIT4) were related to DNA repair, indicating that DNA stability may be influenced by hypoxia in TNBC. Conclusions Our results demonstrate that CAIX appears to be a significant hypoxia-inducible molecular marker and increased CAIX protein levels are independently associated with poor survival in TNBC. Identification of CAIX-linked seven gene-signature and its relationship with enriched cellular functions further support the implication and influence of hypoxia-mediated CAIX expression in TNBC tumour microenvironment.
Related Links	https://breast-cancer-research.biomedcentral.com/counter/pdf/10.1186/s13058-022-01532-0.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13058-022-01532-0
Journal	Breast Cancer Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2022-06-03
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Triple-negative breast cancer Hypoxia Carbonic anhydrase IX TNBC CAIX Prognosis Hypoxia gene panel
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7.1/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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