Expression of the Hypoxia Marker Carbonic Anhydrase 9 Is Associated with Anaplastic Phenotypes in Meningiomas

Abstract Clear cell, microcytic, and angiomatous meningiomas are 3 vasculature-rich variants with overlapping morphological features but different prognostic and treatment implications. Distinction between them is not always straightforward. We compared the expression patterns of the hypoxia marker carbonic anhydrase IX (CA-IX) in meningiomas with predominant clear cell (n = 15), microcystic (n = 9), or angiomatous (n = 11) morphologies, as well as 117 cases of other World Health Organization recognized histological meningioma variants. Immunostaining for SMARCE1 protein, whose loss-of-function has been associated with clear cell meningiomas, was performed on all clear cell meningiomas, and selected variants of meningiomas as controls. All clear cell meningiomas showed absence of CA-IX expression and loss of nuclear SMARCE1 expression. All microcystic and angiomatous meningiomas showed diffuse CA-IX immunoreactivity and retained nuclear SMARCE1 expression. In other meningioma variants, CA-IX was expressed in a hypoxia-restricted pattern and was highly associated with atypical features such as necrosis, small cell change, and focal clear cell change. In conclusion, CA-IX may serve as a useful diagnostic marker in differentiating clear cell, microcystic, and angiomatous meningiomas.

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Mucin 5B, carbonic anhydrase 9 and claudin 18 are potential theranostic markers of gallbladder carcinoma

Histopathology ◽

10.1111/his.13797 ◽

2019 ◽

Vol 74 (4) ◽

pp. 597-607 ◽

Cited By ~ 1

Author(s):

Jaime A Espinoza ◽

Ismael Riquelme ◽

Eduardo A Sagredo ◽

Lorena Rosa ◽

Patricia García ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Gallbladder Carcinoma ◽

Carbonic Anhydrase 9

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The role of extracellular signal-regulated protein kinase in transcriptional regulation of the hypoxia marker carbonic anhydrase IX

Journal of Cellular Biochemistry ◽

10.1002/jcb.20633 ◽

2005 ◽

Vol 97 (1) ◽

pp. 207-216 ◽

Cited By ~ 21

Author(s):

Stefan Kaluz ◽

Milota Kaluzová ◽

Eric J. Stanbridge

Keyword(s):

Transcriptional Regulation ◽

Protein Kinase ◽

Carbonic Anhydrase ◽

Carbonic Anhydrase Ix ◽

Extracellular Signal ◽

Hypoxia Marker

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An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-induced Drug Resistance to Enhance The Efficacy of Myocardial Protection

10.21203/rs.3.rs-216260/v1 ◽

2021 ◽

Author(s):

Wen Zhou ◽

Bin Zhang ◽

Keyu Fan ◽

Xiaojian Yin ◽

Jinfeng Liu ◽

...

Keyword(s):

Drug Resistance ◽

Carbonic Anhydrase ◽

Myocardial Ischemia ◽

Ph Value ◽

Acquired Resistance ◽

Vital Role ◽

Carbonic Anhydrase 9 ◽

Myocardial Hypoxia

Abstract Purpose Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia induced drug resistance.Methods In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.Results Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance, and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.Conclusion Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.

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Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms20020375 ◽

2019 ◽

Vol 20 (2) ◽

pp. 375 ◽

Cited By ~ 8

Author(s):

Alexander W. Eckert ◽

Susanne Horter ◽

Daniel Bethmann ◽

Johanna Kotrba ◽

Tom Kaune ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Regression Analysis ◽

Oral Squamous Cell Carcinoma ◽

Carbonic Anhydrase ◽

Protein Level ◽

Normal Tissue ◽

Mrna Level ◽

Mrna Levels ◽

Cox's Regression ◽

Carbonic Anhydrase 9

s: Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan–Meier and Cox’s regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox’s regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.

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