ArticleDiagnostic pathology2016
Carbonic anhydrase IX is a marker of hypoxia and correlates with higher Gleason scores and ISUP grading in prostate cancer.
Article in Diagnostic pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- Prostate Cancer Imaging Beyond PSMA: Applications of GRPR, AR, and Amino Acid Tracers.Diagnostics (Basel, Switzerland) · 2025Review
- Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.Molecular oncology · 2025Article
- Long-Term Hypoxia Upregulates Wnt and TGFβ1 Signaling in Eccrine Sweat Gland Cells In Vitro.International journal of molecular sciences · 2025Article
- Article
- Systematic Analysis of CA9 as a Pan-Cancer Marker for Prognosis and Immunity.Cancer informatics · 2025Article
- Design and synthesis of chromene-1,2,3-triazole benzene sulfonamide hybrids as potent carbonic anhydrase-IX inhibitors against prostate cancer.RSC medicinal chemistry · 2024Article
- The APE1/REF-1 and the hallmarks of cancer.Molecular biology reports · 2024Review
- Exosome Analysis in Prostate Cancer: How They Can Improve Biomarkers' Performance.Current issues in molecular biology · 2023Review
- Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Expression and prognostic value of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma.BMC urology · 2022Article
- AKT, a Key Transmitter of HIF-1α and AR Signaling Pathways, Has a Critical Role in the Apigetrin-Mediated Anti-Cancer Effects in Prostate Cancer Cells.Biomedicines · 2022Article
- Article
- Role of pH Regulatory Proteins and Dysregulation of pH in Prostate Cancer.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Sodium bicarbonate transporter NBCe1 regulates proliferation and viability of human prostate cancer cells LNCaP and PC3.Oncology reports · 2021Article
- Review
- Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy.Scientific reports · 2021Article
- Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy.Cancers · 2020Review
- Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.Diagnostic pathology · 2020Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCarbonic anhydrase IX is a member of α-carbonic anhydrases that is preferentially expressed in solid tumors. It enables bicarbonate transport across the plasma membrane, neutralizing intracellular pH and conferring to cancer cells a survival advantage in hypoxic/acidic microenvironments. Overexpression of carbonic anhydrase IX in cancer tissues is regulated by hypoxia inducible factor 1α - mediated transcription and the enzyme is considered a marker of tumor hypoxia and poor outcome. The role of carbonic anhydrase IX in prostate cancer has not been fully clarified and controversy has arisen on whether this enzyme is overexpressed in hypoxic prostate cancer tissues.
methodsWe analyzed the expression of carbonic anhydrase IX and hypoxia inducible factor 1α in two prostate cancer cell lines, LNCaP and PC-3, and in 110 cancer biopsies, by western blotting and immunocyto/histochemistry.
resultsIn LNCaP and PC-3 cells, carbonic anhydrase IX was mostly cytoplasmic/nuclear, with very limited membrane localization. Nuclear staining became stronger under hypoxia. When we analyzed carbonic anhydrase IX expression in human prostate cancer biopsies, we found that protein staining positively correlated with hypoxia inducible factor 1α and with Gleason pattern and score, as well as with the novel grading system proposed by the International Society of Urological Pathology for prostate cancer. Once more, carbonic anhydrase IX was mainly cytoplasmic in low grade carcinomas, whereas in high grade tumors was strongly expressed in the nucleus of the neoplastic cell. An association between carbonic anhydrase IX expression level and the main clinic-pathological features involved in prostate cancer aggressiveness was identified.
conclusionsThere was a statistically significant association between carbonic anhydrase IX and hypoxia inducible factor 1α in prostate cancer tissues, that identifies the enzyme as a reliable marker of tumor hypoxia. In addition, carbonic anhydrase IX expression positively correlated with prostate cancer grading and staging, and with outcome, suggesting that the protein may be an independent prognosticator for the disease. The nuclear translocation of the enzyme in hypoxic cancer cells may epitomize a biological switch of the tumor towards a less favorable phenotype.
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