Evidence map›Paper›PMID 35659359›Full record

ArticleBreast cancer research : BCR2022

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

Chong Hui Clara Ong, Dong Yeul Lee, Bernett Lee, Huihua Li, Jeffrey Chun Tatt Lim, Johnathan Xiande Lim, Joe Poh Sheng Yeong, Hiu Yeung Lau, Aye Aye Thike, Puay Hoon Tan and 1 more

Open access · goldAbstract read
In one paragraph

Article in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.

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  6. Garciniagifolone A, derived fromFrontiers in cell and developmental biology · 2026
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  15. Tumor Hypoxia: How Conventional Histology Is Reshaped in Breast Carcinoma.International journal of molecular sciences · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Chong Hui Clara OngHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Dong Yeul LeeHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Bernett LeeAgency of Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN), 8A Biomedical Grove Level 3 & 4. Immunos Building138648, Singapore, Singapore.
Huihua LiDivision of Medicine, Singapore General Hospital, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.
Jeffrey Chun Tatt LimAgency of Science, Technology and Research (A*STAR), Institute of Molecular Cell Biology (IMCB), 61 Biopolis Dr, Singapore, 138673, Singapore.
Johnathan Xiande LimHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Joe Poh Sheng YeongHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Hiu Yeung LauHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Aye Aye ThikeHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Puay Hoon TanHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore.
Jabed IqbalHistopathology Laboratory, Department of Anatomical Pathology, Singapore General Hospital, 20 College Road, Academia, Level 10, Diagnostics Tower, Singapore, 169856, Singapore. jabed.iqbal@singhealth.com.sg.
Singapore General Hospital · SGAgency for Science, Technology and Research · SGDuke-NUS Medical School · SGNanyang Technological University · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

methodsA 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.

resultsForty 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.

conclusionsOur 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.

Indexed as

Breast NeoplasmsCarbonic AnhydrasesTriple Negative Breast NeoplasmsAntigens, NeoplasmBiomarkers, TumorCarbonic Anhydrase IXDNA HelicasesFemaleHumansHypoxiaMultifunctional EnzymesPrognosisRNA HelicasesTumor MicroenvironmentAntigens, NeoplasmBiomarkers, TumorCarbonic Anhydrase IXCarbonic AnhydrasesDNA HelicasesMultifunctional EnzymesRNA HelicasesSETX protein, humanCAIXCarbonic anhydrase IXHypoxiaHypoxia gene panelPrognosisTNBCTriple-negative breast cancer

Identifiers

PMID35659359
PMCPMC9164406
OpenAlexW4281774394

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.