Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection

Jeng, Kuo‐Shyang; Sheen, I‐Shyan; Wang, Yi‐Ching; Gu, Shi; Chu, Chien‐Ming; Shih, Shou‐Chuan; Wang, Po-Chuan; Chang, Wen-Hsing; Wang, Horng‐Yuan

doi:10.3748/wjg.v10.i5.676

Cited by 28 publications

(14 citation statements)

References 56 publications

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“…In total, there were four tissue OS studies (Chow et al, 1997;Jeng et al, 2004a;Deli et al, 2005;Sheen et al, 2005), six tissue DFS studies (Jeng et al, 2004a;Sheen et al, 2005;Guo et al, 2006;Wada et al, 2006;Zhang et al, 2006;Ho et al, 2007), seven serum OS studies (Poon et al, 2001(Poon et al, , 2004a(Poon et al, , b, 2007Chao et al, 2003;Kim et al, 2004;Jeng et al, 2004b;Treiber et al, 2006), and five serum DFS studies (Poon et al, 2001(Poon et al, , 2007Chao et al, 2003;Jeng et al, 2004b;Treiber et al, 2006). Pooled HRs were then calculated for all groups.…”

Section: Summary Estimates Of Primary Studiesmentioning

confidence: 99%

“…Although not entirely unexpected given the high burden of HCC in Asian populations (El-Serag, 2002), this raises a question regarding external validity of results and applicability to Western societies. However, multiple tissue (Jeng et al, 2004a;Sheen et al, 2005;Ho et al, 2007) and serum (Poon et al, 2001(Poon et al, , 2004a studies failed to find a relationship between chronic viral hepatitis status and VEGF levels. This is somewhat reassuring given the high prevalence of this liver disease aetiology in Asia.…”

Section: Test For Heterogeneitymentioning

confidence: 99%

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Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

et al. 2009

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Hepatocellular carcinoma (HCC) is a highly vascular tumour that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC. Its overall test performance remains unclear, however. The aim was to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of VEGF as a predictor of survival in patients with treated HCC. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing disease-free and overall survival in patients with high VEGF levels as compared to those with low levels. Studies were pooled and summary hazard ratios were calculated. A total of 16 studies were included for meta-analysis (8 for tissue and 8 for serum). Methodological analysis indicated a trend for higher study quality with serum studies as compared to tissue-based investigations. Four distinct groups were pooled for analysis: tissue overall survival ( n =251), tissue disease-free survival ( n =413), serum overall survival ( n =579), and serum disease-free survival ( n =439). High tissue VEGF levels predicted poor overall (HR=2.15, 95% CI: 1.26–3.68) and disease-free (HR=1.69, 95% CI: 1.23–2.33) survival. Similarly, high serum VEGF levels predicted poor overall (HR=2.35, 95% CI: 1.80–3.07) and disease-free (HR=2.36, 95% CI 1.76–3.16) survival. A high degree of inter-study consistency was present in three of four groups analysed. Tissue and serum VEGF levels appear to have significant predictive ability for estimating overall survival in HCC and may be useful for defining prognosis in HCC.

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Section: Summary Estimates Of Primary Studiesmentioning

confidence: 99%

Section: Test For Heterogeneitymentioning

confidence: 99%

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

et al. 2009

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“…Kwak et al 20 also found that tumor size was negatively correlated with immunohistochemical VEGF expression. Meanwhile, Jeng et al 21 found that the level of VEGF mRNA in HCC tissues did not significantly correlate with tumor size, cellular differentiation, capsule, daughter nodules, vascular permeation, necrosis, and hemorrhage of tumors. Ng et al 22 similarly reported that there was no statistically significant association between tumor VEGF mRNA levels and tumor size or other pathologic features.…”

Section: Pathologic Tumor Size and Vascular Endothelial Growth Factormentioning

confidence: 99%

Magnetic Resonance Imaging and Expression of Vascular Endothelial Growth Factor in Hepatocellular Nodules in Cirrhosis and Hepatocellular Carcinomas

Kanematsu

Semelka²,

Osada

et al. 2005

Topics in Magnetic Resonance Imaging

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We summarized and discussed our previous research results on correlation between magnetic resonance (MR) imaging findings and vascular endothelial growth factor (VEGF) expression in benign or borderline hepatocellular nodules in cirrhosis, hepatocellular carcinomas (HCCs), and in the surrounding liver. Magnetic resonance images were retrospectively correlated quantitatively and qualitatively with VEGF expression in hepatic nodules and in the surrounding liver. By immunohistochemistry, hepatic nodules with moderate to strong immunoreactivity for VEGF showed higher T1 signal intensity, and those with intense immunoreactivity for VEGF showed higher T2 signal intensity. By Western blotting, HCC-to-liver contrast-to-noise ratio correlated with VEGF indices (VEGFs) of hepatocellular carcinomas inversely on opposed-phase T1-weighted, directly on T2-weighted, and marginally and inversely on gadolinium-enhanced hepatic arterial-phase images. On T2-weighted images, standard-deviation ratio of hepatocellular carcinomas correlated directly with VEGFs of hepatocellular carcinomas. Heterogeneities of hepatocellular carcinomas on MR images correlated directly with VEGFs of HCCs on opposed-phase T1-weighted, T2-weighted, hepatic arterial-phase, and equilibrium-phase images. Our results may reflect that MR signal intensity, hepatic arterial vascularity, and heterogeneity of hepatocellular nodules on MR images are closely related to the intensity of VEGF expression as up-regulated by hyper- or hypoxia in the nodules. Gadolinium-enhanced MR imaging may be useful to monitor ischemic state of hepatocelluar nodules. Although real impacts of our results on radiologic practice have been still debatable, we believe that our results may help future radiologic practice in conjunction with biomolecular or genetic treatments for hepatocellular carcinomas.

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“…42,[44][45][46][47] Moreover, high VEGF levels in HCC tissue samples are associated with rapid recurrence after resection. [48][49][50] Finally, it was recently reported that the multikinase inhibitor sorafenib increases tumoral VEGF expression, which might represent a potential road to resistance. 29,51 Hence, combination of RFA, TACE, or sorafenib with a drug that has the potential to reduce VEGF production, such as GDC-0449, might improve the efficacy of these treatment modalities.…”

Section: Discussionmentioning

confidence: 99%

Hedgehog inhibition reduces angiogenesis by downregulation of tumoral VEGF‐A expression in hepatocellular carcinoma

et al. 2013

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Background: Dysregulation and activation of Hedgehog (Hh) signalling may contribute to tumorigenesis, angiogenesis, and metastatic seeding in several solid tumours. Objective: We investigated the impact of Hh inhibition on tumour growth and angiogenesis using in-vitro and in-vivo models of hepatocellular carcinoma (HCC). Methods: The effect of the Hh pathway inhibitor GDC-0449 on tumour growth was investigated using an orthotopic rat model. Effects on angiogenesis were determined by immunohistochemical staining of von Willebrand factor antigen and by assessing the mRNA expression of several angiogenic factors. In vitro, HCC cell lines were treated with GDC-0449 and evaluated for viability and expression of vascular endothelial growth factor (VEGF). Endothelial cells were evaluated for viability, migration, and tube formation. Results: In the orthotopic HCC model, GDC-0449 significantly decreased tumoral VEGF expression which was accompanied by a significant reduction of microvessel density and tumour growth. In HCC cells, GDC-0449 had no effect on cell growth but significantly reduced target gene regulation and VEGF expression while having no direct effect on endothelial cell viability, migration, and tube formation. Conclusions: Hh inhibition with GDC-0449 downregulates tumoral VEGF production in vitro and reduces tumoral VEGF expression, angiogenesis, and tumour growth in an orthotopic HCC model.

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Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection

Abstract: The expression of VEGF mRNA, especially isoform VEGF(165), in HCC tissues, may play a significant and independent role in the prediction of postoperative recurrence of HCC.

Cited by 28 publications

References 56 publications

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

Magnetic Resonance Imaging and Expression of Vascular Endothelial Growth Factor in Hepatocellular Nodules in Cirrhosis and Hepatocellular Carcinomas

Hedgehog inhibition reduces angiogenesis by downregulation of tumoral VEGF‐A expression in hepatocellular carcinoma

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