Description of 2 angiogenic phenotypes in clear cell renal cell carcinoma

Edeline, Julien; Mottier, Stéphanie; Vigneau, Cécile; Jouan, Florence; Perrin, Christophe; Zerrouki, S.; Fergelot, Patricia; Patard, Jean‐Jacques; Rioux‐Leclercq, Nathalie

doi:10.1016/j.humpath.2012.01.023

Cited by 38 publications

(32 citation statements)

References 32 publications

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“…A screen of the titles and abstracts identified 50 papers eligible for the assessment of the prognostic value of CAIX status in patients with RCC. After carefully review of each of the 50 studies, certain studies were excluded for the following rationale: six studies evaluated CAIX status by enzyme-linked immunosorbent assay (ELISA) [23], [24], [25], [26], [27], [28]; five studies evaluated CAIX status by real-time-PCR [29], [30], [31], [32], [33]; one study was on the topic of a single nucleotide polymorphism in the CAIX gene [34]; fourteen studies did not report survival outcome on CAIX expression or survival outcome could not be extracted [17], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47]; and nine studies contained overlapping data with other studies by the same authors or institutions [48], [49], [50], [51], [52], [53], [54], [55], [56]. Thus, fifteen papers were included in our meta-analysis to evaluate the relationship between CAIX expression and prognosis in patients with renal cell carcinoma [16], [18], [19], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68].…”

Section: Resultsmentioning

confidence: 99%

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

Zhao

Liao

et al. 2014

PLoS ONE

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BackgroundCarbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with renal cell carcinoma (RCC). The prognostic value of CAIX in RCC however, remains inconclusive according to published works. This study aimed to analyze CAIX as a biological marker to predict RCC patient prognosis.MethodsA literature search of the PubMed and Web of Knowledge databases was performed to retrieve original studies from their inception to December of 2013. Fifteen studies, collectively including a total of 2611 patients with renal cell carcinoma, were carefully reviewed. Standard meta-analysis methods were applied to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio (HR) and its 95% confidence interval (CI) were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Review Manager 5.2 software and Stata software 11.0.ResultsIn patients with RCC, low CAIX expression was associated with poor disease-specific survival (HR = 1.89, 95% CI: 1.20–2.98, P = 0.006), unfavorable progression-free survival (HR = 2.62, 95% CI: 1.14–6.05, P = 0.02) and worse overall survival (HR = 2.03, 95% CI: 1.28–3.21, P = 0.002). Furthermore, low CAIX expression was significantly associated with the presence of lymph node metastases (odds ratio (OR) = 0.31, 95% CI = 0.15–0.62, P = 0.0009) and distant metastases (OR = 0.66, 95% CI = 0.46–0.96, P = 0.03) and predicted a higher tumor grade (OR = 0.41, 95% CI = 0.31–0.54, P<0.00001).ConclusionsLow CAIX expression most likely indicates poor prognosis in RCC patients. Moreover, low CAIX expression was significantly associated with unfavorable clinicopathological factors. To strengthen our findings, further well-designed prospective studies should be conducted to investigate the role of CAIX expression in RCC.

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Section: Resultsmentioning

confidence: 99%

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

Zhao

Liao

et al. 2014

PLoS ONE

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“…We also observe an immature vasculature in the tumors expressing pVHL 172 ( Supplementary Figure 5 ). As previously mentioned, tumor vessels remain immature and lack the tight association between mural cells and endothelial tubes dependent on the excessive VEGF synthesis [ 24 , 25 ]. Moreover, sarcomatoid differentiation usually arises within high-grade ccRCC representing a late step in the progression of this tumor type [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of pro-tumorigenic genes includingTGFB1andMMP13

Hascoet¹,

Chesnel²,

Jouan³

et al. 2017

Oncotarget

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The von Hippel-Lindau (VHL) tumor suppressor gene is often deleted or mutated in ccRCC (clear cell renal cell carcinoma) producing a non-functional protein. The gene encodes two mRNA, and three protein isoforms (pVHL213, pVHL160 and pVHL172). The pVHL protein is part of an E3 ligase complex involved in the ubiquitination and proteasomal degradation of different proteins, particularly hypoxia inducible factors (HIF) that drive the transcription of genes involved in the regulation of cell proliferation, angiogenesis or extracellular matrix remodelling. Other non-canonical (HIF-independent) pVHL functions have been described. A recent work reported the expression of the uncharacterized protein isoform pVHL172 which is translated from the variant 2 by alternative splicing of the exon 2. This splice variant is sometimes enriched in the ccRCCs and the protein has been identified in the respective samples of ccRCCs and different renal cell lines. Functional studies on pVHL have only concerned the pVHL213 and pVHL160 isoforms, but no function was assigned to pVHL172. Here we show that pVHL172 stable expression in renal cancer cells does not regulate the level of HIF, exacerbates tumorigenicity when 786-O-pVHL172 cells were xenografted in mice. The pVHL172-induced tumors developed a sarcomatoid phenotype. Moreover, pVHL172 expression was shown to up regulate a subset of pro-tumorigenic genes including TGFB1, MMP1 and MMP13. In summary we identified that pVHL172 is not a tumor suppressor. Furthermore our findings suggest an antagonistic function of this pVHL isoform in the HIF-independent aggressiveness of renal tumors compared to pVHL213.

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“…Moreover, Edeline et al demonstrated two different angiogenic phenotype described as mature and immature. These two patterns could coexist within the same tumour demonstrating the heterogeneity of the vascular component [32]. Dufies et al demonstrated in experimental tumours that sunitinib stimulated the development of lymphatic vessels.…”

Section: Vascular Componentmentioning

confidence: 98%

Immunotherapy in Renal Cell Carcinoma: The Future Is Now

Deleuze

Saout

Dugay

et al. 2020

IJMS

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168

132

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Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent need to identify biomarkers in order to predict the efficacy of drugs and to better stratify patients. Owing to the limitations of programmed death-ligand 1 (PD-L1), the most studied immunohistochemistry biomarkers, and of the tumor mutational burden, the identification of more reliable markers is an unmet need. New technologies could help in this purpose.

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Description of 2 angiogenic phenotypes in clear cell renal cell carcinoma

Cited by 38 publications

References 32 publications

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

The pVHL172 isoform is not a tumor suppressor and up-regulates a subset of pro-tumorigenic genes includingTGFB1andMMP13

Immunotherapy in Renal Cell Carcinoma: The Future Is Now

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