<i>MN/CA9</i> gene expression as a potential biomarker in renal cell carcinoma

Murakami, Y.; Kanda, Kazuya; Tsuji, Masaaki; Kanayama, Hiro‐omi; Kagawa, Shunsuke

doi:10.1046/j.1464-410x.1999.00007.x

Cited by 48 publications

(23 citation statements)

References 15 publications

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“…Again with high tumor grade there was a high rate of low expression (81.8%). These outcomes are again consistent with the previous literature [10][11][12]14]. When the cumulative survival rate was correlated with the tumor grade, stage and CA9 expression, CA9 expression was at least as good a factor effecting survival rate as T stage and tumor grade.…”

Section: Discussionsupporting

confidence: 92%

“…In the CCC group, the staining rate was 91%. Murakami et al [10] found CA9 expression in CCC to be 92%; this rate in the paper by Bui et al [15] was reported to be 94%.…”

Section: Discussionmentioning

confidence: 89%

“…Previous studies have shown that CA9, a member of the carbonic anhydrase family, is induced constitutively in certain tumor types but is absent in most normal tissues with the exception of epithelial cells of the gastric mucosa [7][8][9][10]. Furthermore, previous immunobiochemical studies of malignant and benign renal tissues revealed that CA9 is also highly expressed in RCC, suggesting that CA9 expression may be a useful diagnostic biomarker [11][12].…”

Section: Introductionmentioning

confidence: 99%

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CA9 Expression as a Prognostic Factor in Renal Clear Cell Carcinoma

Soyupak

Erdoğan²,

Ergïn³

et al. 2005

Urol Int

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Introduction: We investigated whether CA9 protein could be used as a prognostic tumor marker as well as a diagnostic biomarker in renal clear cell carcinoma. Materials and Methods: Nephrectomy specimens from 92 patients were used in this study. 80 of these were renal cell carcinomas, 10 adenomas and 2 oncocytomas. Of the renal cell carcinomas, 67 were clear cell carcinomas. Immunohistochemical analysis using CA9 monoclonal antibody (M75) was performed on paraffin-embedded specimens. CA9 staining was correlated with tumor stage, grade, lymph node involvement, distant metastasis and cumulative survival time. Results: CA9 was present in 91.2% of clear cell carcinomas. Low staining was a poor prognostic factor, and conversely high staining a good prognostic one. CA9 expression was found to be the best prognostic factor when compared with T stage and grade. Even in low-grade and stage tumors, the presence of low expression correlated with lowered survival times. Conclusions: On the basis of our study, CA9 is a significant molecular marker in renal clear cell carcinomas. Decreased CA9 expression is independently associated with poor survival. CA9 can be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CA9 targeted therapies.

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Section: Discussionsupporting

confidence: 92%

“…In the CCC group, the staining rate was 91%. Murakami et al [10] found CA9 expression in CCC to be 92%; this rate in the paper by Bui et al [15] was reported to be 94%.…”

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CA9 Expression as a Prognostic Factor in Renal Clear Cell Carcinoma

Soyupak

Erdoğan²,

Ergïn³

et al. 2005

Urol Int

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“…CA-IX is an HIF-a target gene that is frequently expressed in RCC but very rarely detected in normal kidney tissue (27). We observed an overexpression of CA-IX in all but one ccRCC samples.…”

Section: Discussionmentioning

confidence: 59%

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

Dannenmann

Hermanns

Bransi

et al. 2013

Cancer Immunology Research

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Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of MAGE-A9 and NY-ESO-1 in 36% and 55% of samples, respectively, and overexpression of PRAME, RAGE-1, CA-IX, Cyclin D1, ADFP, C-MET, and RGS-5 in many of the tumor samples. We analyzed the blood of patients with HLA-A2 þ ccRCC for the presence of CD8 þ T cells specific for TAA-derived HLA-A2-restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with Cyclin D1-positive tumors. Cyclin D1-specific CD8 þ T cells secreted TNF-a, IFN-g, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8 þ T cells in the blood of these patients with ccRCC. The high frequency (43%) of Cyclin D1 overexpression and the presence of functional cyclin D1-specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies. Cancer Immunol Res; 1(5); 288-95. Ó2013 AACR.

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“…17 Of these enzymes, CA IX is a membrane bound version and its over-expression on the cell surface is seen in a number of solid tumors, particularly in clear cell RCC and including cervical, ovarian, colorectal, head and neck, bladder and non-small cell lung carcinomas. 18,19 In all these malignancies, the expression of CA IX is invariably linked to the development of tumor hypoxia which is mediated by the transcription factor HIF-1.…”

Section: Introductionmentioning

confidence: 99%

366 Carbonic Anhydrase Ix Shedding Through Exosomes in Renal Carcinoma Cells

Dorai

2010

Journal of Urology

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Carbonic anhydrase IX (CA IX) is a transmembrane glycoprotein highly expressed in clear cell carcinoma of the kidney and in a wide variety of other human cancers. Its expression is largely under the control of intratumoral hypoxia and in some subtypes of renal cell carcinoma (RCC), by the presence of a defective version of the von Hippel Lindau (VHL) gene by which the HIF-1α factor is stabilized. Several notable studies have shown that CA IX is involved in the control of acidity intracellularly. Thus, this enzyme could be involved in the regulation of pH within the tumor and may modulate the tumor microenvironment. Recent studies have also shown that this enzyme could be involved in the control of cell adhesion processes between the cancer cells, contributing to their invasive potential. Here, we have analyzed the effect of increasing the level of CA IX expression in the CA IX negative SKRC-17 renal cancer cells. Our results showed that CA IX is recruited to the lipid rafts of these cancer cells. Our results also highly suggest that the lipid raft component gangliosides are shed in the form of exosomes in this model system as a result of forced CA IX expression. The level of ganglioside shedding positively correlated with the increased level of CA IX expression in these cells. Finally, from a glycobiological perspective, our results indicate that elevated levels of CA IX expression contributes to increased ganglioside shedding in the form of exosomes which in turn may contribute to increased invasiveness and immunological escape in this malignancy.

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MN/CA9 gene expression as a potential biomarker in renal cell carcinoma

Abstract: These results suggest that MN/CA9 expression is a potential diagnostic biomarker of RCC, especially the clear-cell type, and can be targeted using molecular biological techniques.

Cited by 48 publications

References 15 publications

CA9 Expression as a Prognostic Factor in Renal Clear Cell Carcinoma

CA9 Expression as a Prognostic Factor in Renal Clear Cell Carcinoma

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

366 Carbonic Anhydrase Ix Shedding Through Exosomes in Renal Carcinoma Cells

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