Preoperative high levels of serum vascular endothelial growth factor are a prognostic marker for poor outcome after surgical treatment of renal cell carcinoma

Guðbrandsdottir, Gigja; Hjelle, Karin M.; Frugård, Jannicke; Bostad, Leif; Aarstad, Hans Jørgen; Beisland, Christian

doi:10.3109/21681805.2015.1021833

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…VEGF has been investigated thoroughly for prognostic impact on the clinical outcome of RCC. Clinically, high levels of blood or intratumoral VEGF have been shown to be associated with an advanced stage of disease and a worse prognosis for RCC due to alterations in VHL gene and subsequent accumulation of the transcription factor HIF1α at protein level . Novel therapies have been developed targeting VEGF signaling by either targeting the VEGF‐A ligand (Bevacizumab), inhibiting the multityrosine kinase receptor (Sunitinib, Sorafenib and Pazopanib) (TKIs) or inhibiting the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway (Temsirolimus and Everolimus) .…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

Rabjerg

Bjerregaard

Halekoh

et al. 2016

APMIS

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The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan® Array, could identify superior prognostic messenger RNA (mRNA)s in long-term follow-up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with ccRCC. Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK2A1 was a strong indicator of a poor overall survival (OS) (HR = 5.01, p< 0.001), disease specific survival (DSS) (HR = 6.21, p = 0.007) and progression free survival (PFS) (HR = 5.93, p = 0.005). High expression of SPP1 was associated to poor PFS (HR = 4.41, p = 0.04). DEFB1 was associated with a better PFS (HR = 0.24, p = 0.006). In multivariate analysis, CSNK2A1 was associated to a worse OS (HR = 3.56, p = 0.008) and PFS (HR = 3.84, p = 0.005), whereas SPP1 was an independent predictor of a worse PFS (HR = 3.46, p = 0.007) and DEFB1 of a better PFS (HR = 0.37, p = 0.027). These results show that with TaqMan®) Array we could identify three superior gene products related to prognosis. Further studies are needed to elucidate the pathways and roles of these genes in renal cacer development.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

Rabjerg

Bjerregaard

Halekoh

et al. 2016

APMIS

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“…For example, a recent study that was included in the current meta-analysis examined 124 patients with RCC that was surgically treated, and found that tumor stage and a high VEGF level were predictors of recurrence and cancer-specific death, and that serum VEGF level may be useful for determining RCC subtype prior to surgery [11]. On the other hand, earlier studies have shown that VEGF levels were not associated with cause-specific survival [12], only provided prognostic information for patients with a good performance status (2 or 3) [13], or only identified patients with aggressive disease [40].…”

Section: Discussionmentioning

confidence: 99%

“…Only three studies [11,30,32] provided HR data, or data from which the HR could be calculated, and were included in the analysis of OS. Relatively high heterogeneity was observed among the three studies; therefore, a random-effects model of analysis was used (Q statistic = 11.249, I 2 = 82.22%, p = 0.004).…”

Section: Serum Vegf Levelmentioning

confidence: 99%

“…Study has shown that VEGF expression is correlated with tumor grade, size, and disease stage, lymph node involvement, vascular invasion, and poor survival in patients with RCC [9,10]. Recent study has shown that a high serum VEGF level is associated with an increased risk of recurrence and cancer-specific death in patients with RCC [11]. On the other hand, earlier studies did not find an association with VEGF level and RCC prognosis [12,13].…”

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confidence: 99%

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The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis

Shen

Liu

et al. 2017

CIM

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Objective: Vascular endothelial growth factor (VEGF) serum level or tumor expression may be prognostic in renal cell carcinoma (RCC). The purpose of this meta-analysis was to examine the prognostic value of serum VEGF level and tumor expression in patients with RCC.Methods: PubMed and EMBASE databases were searched until September 26, 2016. Prospective and retrospective studies of RCC patients that had VEGF levels measured were included. Outcome measures were overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS).Results: A total of 14 studies were included in the meta-analysis. In patients with RCC, elevated serum VEGF level was not associated with OS (pooled hazard ratio [HR] = 1.16; 95% confidence interval [CI]: 0.52 to 2.60; p = 0.716), but was associated with poor DSS (pooled HR = 4.22; 95% CI: 2.02 to 8.79; p < 0.001) and PFS (pooled HR = 1.50; 95% CI: 1.22 to 1.85; p < 0.001). Removal of one study, however, resulted in elevated serum level being associated with poorer OS. Tumor VEGF expression was not associated with OS (pooled HR = 1.48; 95% CI: 0.74 to 2.95; p = 0.263), but was associated with worse DSS (pooled HR = 1.83; 95% CI: 1.24 to 2.71; p = 0.003). Conclusion:In patients with RCC, elevated serum VEGF level is associated with worse OS, DSS, and PFS, while tumor expression is only associated with worse DSS. The number of studies, however, was limited and the results should be interpreted with caution.

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“…Vascular endothelial growth factor pathway is reported to play a conspicuous role in the growth and progression of human cancers, such as renal cell carcinoma. 5 – 7 VEGF +405G>C, VEGF −634G>C, VEGF −460T>C, VEGF +936C>T, VEGF −2578 C>A, VEGF −1154 G>A, VEGF +1612 G>A gene polymorphisms were the important gene types for VEGF. The current evidences indicate that VEGF +405G>C, VEGF −634G>C, VEGF −460T>C, VEGF +936C>T, VEGF −2578 C>A, VEGF −1154 G>A, and VEGF +1612 G>A gene polymorphisms might take part in the pathogenesis of carcinogenesis.…”

Section: Introductionmentioning

confidence: 96%

Association of Vascular Endothelial Growth Factor Gene Polymorphism With Renal Cell Carcinoma Risk

Zhou

Kang

Wang

et al. 2017

Technol Cancer Res Treat

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The conclusion of the relationship between vascular endothelial growth factor gene polymorphism and renal cell carcinoma risk was inconsistent. This study was performed to assess the relationship between vascular endothelial growth factor gene polymorphism and renal cell carcinoma risk using meta-analysis. The association studies were identified from PubMed, Embase, and Web of Science, and eligible studies were included and calculated. Ten studies were included for this meta-analysis. vascular endothelial growth factor (VEGF) +405G > CC allele and GG genotype were associated with renal cell carcinoma risk for overall populations in this meta-analysis (C allele: odds ratio = 1.18, 95% confidence interval: 1.05-1.33, P = .004; CC genotype: odds ratio = 1.20, 95% confidence interval: 0.96-1.50, P = .12; GG genotype: odds ratio = 0.79, 95% confidence interval: 0.67-0.93, P = .004). Furthermore, VEGF +936C>T gene polymorphism and VEGF −2578 C>A gene polymorphism were associated with renal cell carcinoma risk for overall populations (+936C>T: T allele: odds ratio = 1.16, 95% confidence interval: 1.05-1.29, P = .004; TT genotype: odds ratio = 1.25, 95% confidence interval: 1.02-1.52, P = .03; CC genotype: odds ratio = 0.86, 95% confidence interval: 0.75-0.98, P = .03; −2578 C>A: A allele: odds ratio = 1.26, 95% confidence interval: 1.15-1.38, P < .00001; AA genotype: odds ratio = 1.39, 95% confidence interval: 1.16-1.67, P = .0004; CC genotype: odds ratio = 0.75, 95% confidence interval: 0.61-0.92, P = .006). However, VEGF −634G>C, VEGF −460T>C, VEGF −1154 G>A, and VEGF +1612 G>A gene polymorphisms were not associated with renal cell carcinoma risk. In conclusion, VEGF +405G>CC allele and GG genotype, VEGF +936C>T gene polymorphism, and VEGF −2578 C>A gene polymorphism were associated with renal cell carcinoma risk for overall populations. However, more studies should be performed to assess this relationship in the future.

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Preoperative high levels of serum vascular endothelial growth factor are a prognostic marker for poor outcome after surgical treatment of renal cell carcinoma

Abstract: Tumour stage and a high level of serum VEGF were predictors for an increased risk of recurrence and cancer-specific death. Furthermore, the study showed that serum VEGF may be used to determine the subtype of RCC preoperatively.

Cited by 11 publications

References 24 publications

Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers

The prognostic value of vascular endothelial growth factor in patients with renal cell carcinoma: a systematic review of the literature and meta-analysis

Association of Vascular Endothelial Growth Factor Gene Polymorphism With Renal Cell Carcinoma Risk

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