Prognostic Significance of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery

Chao, Yee; Li, Chung-Ping; Chau, Gar‐Yang; Chen, Chih‐Ping; King, Kuang‐Liang; Lui, Wing‐Yiu; Yen, Sang‐Hue; Chang, Full‐Young; Chan, Wing‐Kai; Lee, Shou‐Dong

doi:10.1245/aso.2003.10.002

Cited by 194 publications

(112 citation statements)

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“…It has been reported previously that in normal liver cells, the level and intensity of VEGF is not detectable (4,18,30,32). We found that VEGF was undetectable in the low-grade HCC tumors that we assayed.…”

Section: Expression Levels Of Prb2/p130 P27mentioning

confidence: 90%

“…Usually, HCC arises from an adenomatous hyperplasia in an already diseased liver and progresses from a well-differentiated stage to less-differentiated forms (3). Ordinary HCCs formed by progression show highly increased cellular proliferation, neovascularization, production of basic fibroblast growth factor, and aneuploidy in some tumors (4). Corresponding to its malignant progression, HCCs show loss of heterozygosity for multiple chromosomes (5).…”

Section: Introductionmentioning

confidence: 99%

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pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

Claudio

Russo

Kumar

et al. 2004

Clinical Cancer Research

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Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million fatalities occurring annually worldwide. Multiple risk factors are associated with HCC disease etiology, the highest incidence being in patients with chronic hepatitis B virus and hepatitis C virus, although other factors such as genetic makeup and environmental exposure are involved. Multiple genetic alterations including the activation of oncogenes and inactivation of tumor suppressor genes are required for malignancy in human cancers and are correlated with increased stages of carcinogenesis and further tumor progression. In this study of 21 HCC patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF), p27 (KIP1) , and proliferating cell nuclear antigen as potential HCC molecular biomarkers. In our sample set, we found that p27 (KIP1) was absent. Univariate survival analysis showed that proliferating cell nuclear antigen expression (diffuse staining >50% of positive cells in tumor) was confirmed as a significant HCC prognostic biomarker for determining patient survival agreeing with previous studies (P ‫؍‬ 0.0126, log-rank test). Lower pRb2/p130 expression was associated to a borderline P value of inverse correlation with tumor malignancy and to a positive correlation with respect to the time from HCC diagnosis (Spearman coefficient ‫؍‬ 0.568; P < 0.05). Conversely, higher VEGF expression was associated with a poor survival (P ‫؍‬ 0.0257, log-rank test). We demonstrate for the first time that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (P < 0.05) in p27 (KIP1) -negative HCC patients. pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Furthermore, we have evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a p27 (KIP1) -independent manner. Additional studies with larger numbers of patient data would allow the use of multivariable techniques and would be able to further identify patients with poorer survival.

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Section: Expression Levels Of Prb2/p130 P27mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

Claudio

Russo

Kumar

et al. 2004

Clinical Cancer Research

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“…Furthermore, increased VEGF expression has been reported in cirrhotic and dysplastic liver tissue, suggesting a possible role for VEGF-mediated angiogenesis in hepatocarcinogenesis (El-Assal et al, 1998). VEGF clearly has an important regulatory role in HCC; high levels of VEGF expression have been linked with HCC tumor grade , poor outcome after resection (Poon et al, 2004b), disease recurrence, poor disease-free and overall survival (OS) (Chao et al, 2003), vascular invasion (Li et al, 1998) and portal vein emboli (Zhou et al, 2000).…”

Section: Vegf Receptor Signalingmentioning

confidence: 99%

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

2010

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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%

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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Prognostic Significance of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery

Abstract: Preoperative serum VEGF is a significant independent predictor of tumor recurrence, DFS, and OS in patients with resectable HCC.

Cited by 194 publications

References 38 publications

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

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

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