Recurrence and Poor Prognosis Following Resection of Small Hepatitis B-Related Hepatocellular Carcinoma Lesions Are Associated with Aberrant Tumor Expression Profiles of Glypican 3 and Osteopontin

Yu, Ming; Lee, Yun Shien; Lin, Sey‐En; Wu, Hsiang Yao; Chen, Tse Ching; Lee, Wei Chen; Chen, Miin Fu; Tsai, Chia-Lung

doi:10.1245/s10434-011-1946-2

Cited by 37 publications

(33 citation statements)

References 47 publications

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“…Overexpression of OPN is found to lead to intrahepatic metastasis, early recurrence and poorer prognosis of surgically resected HCC 77, 78. Similarly, OPN positive expression facilitates recurrence and reduces patient survival after liver transplantation for HCC 79.…”

Section: Opn In Hepatocellular Carcinomamentioning

confidence: 99%

Role of Osteopontin in Liver Diseases

et al. 2016

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Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells. OPN is highlighted as a chemoattractant for macrophages and neutrophils during injury in inflammatory liver diseases. OPN activates hepatic stellate cells (HSCs) to exert an enhancer in fibrogenesis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interests, especially with regards to its role as a diagnostic and prognostic factor. Interestingly, OPN acts an opposing role in liver repair under different pathological conditions. This review summarizes the current understanding of OPN in liver diseases. Further understanding of the pathophysiological role of OPN in cellular interactions and molecular mechanisms associated with hepatic inflammation, fibrosis and cancer may contribute to the development of novel strategies for clinical diagnosis, monitoring and therapy of liver diseases.

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Section: Opn In Hepatocellular Carcinomamentioning

confidence: 99%

Role of Osteopontin in Liver Diseases

et al. 2016

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“…In our earlier study, we have established a dataset for early stage HBV-HCC (<5 cm) patients (n=20) by using Affymetrix U133A oligonucleotide microarray (15). We then took the advantage of this dataset and tried to search for potential genes that might be correlated with CK19 expression.…”

Section: Microarray Data Mining and Immunohistochemical Studymentioning

confidence: 99%

Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19‑positive hepatocellular carcinoma

et al. 2017

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Abstract.A previous study demonstrated that cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) is an indicator of HCC invasiveness, including lymph node metastasis (LNM), tumor infiltration/non-encapsulation and poor prognosis. The exact mechanism by which CK19 expression results in poor prognosis remains unclear. Through the use of an Affymetrix U133A oligonucleotide microarray [20 patients with hepatitis B virus (HBV)-HCC], it was demonstrated that cadherin 17 (CDH17) significantly correlated with CK19 expression (R 2 , 0.867; P<0.001) in HBV-HCC. Immunohistochemical analysis (114 patients with HBV-HCC) also demonstrated a significant correlation between CK19 and CDH17 expressions in primary tumor tissue (R 2 , 0.414; P<0.001). In addition, CK19 and CDH17 expressions levels revealed a significant association with LNM (P<0.001). Cox regression multivariate analysis demonstrated that indocyanine green retention at 15 min >10% and CDH17 expression were independent prognostic factors for disease free survival (P=0.010 and 0.002, respectively). In vitro studies showed that epidermal growth factor can induce the expression of both CK19 and CDH17, and CDH17 in turn can enhance the expression of CK19 in HCC. In summary, this study demonstrated that the early recurrence and poor prognosis of CK19(+) HCC may be due to the expression of CDH17, a gene known to be associated with vascular invasion, tumor metastasis, and advanced tumor stage of HCC. Thus, novel therapeutics by targeting CDH17 may be beneficial for CK19(+) HCC.

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“…IGF2, a member of the insulin-like growth factor family with potent mitogenic effects, has been correlated with degree of differentiation, infiltration of serosa, size of tumor, and proliferative index of the tumor [135–141]. OPN, a protein known to be an important modulator of inflammatory cascades, has been shown to be predictive of worse disease-free and overall survival, as well as correlating with severity of liver damage, capsular infiltration, venous invasion, and lymph node metastases [142–146]. …”

Section: Non-cellular Factors In the Hbv-associated Hcc Microenvironmentmentioning

confidence: 99%

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

Yang

Markowitz

Wang

2014

National Science Review

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In contrast to a majority of cancer types, the initiation of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue, with one of the most prevalent etiological factors being hepatitis B virus (HBV). Transformation of the liver in HBV-associated HCC often follows from or accompanies long-term symptoms of chronic hepatitis, inflammation and cirrhosis, and viral load is a strong predictor for both incidence and progression of HCC. Besides aiding in transformation, HBV plays a crucial role in modulating the accumulation and activation of both cellular components of the microenvironment, such as immune cells and fibroblasts, and non-cellular components of the microenvironment, such as cytokines and growth factors, markedly influencing disease progression and prognosis. This review will explore some of these components and mechanisms to demonstrate both underlying themes and the inherent complexity of these interacting systems in the initiation, progression, and metastasis of HBV-positive HCC.

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Recurrence and Poor Prognosis Following Resection of Small Hepatitis B-Related Hepatocellular Carcinoma Lesions Are Associated with Aberrant Tumor Expression Profiles of Glypican 3 and Osteopontin

Abstract: Elevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection.

Cited by 37 publications

References 47 publications

Role of Osteopontin in Liver Diseases

Role of Osteopontin in Liver Diseases

Cadherin 17 is related to recurrence and poor prognosis of cytokeratin 19‑positive hepatocellular carcinoma

The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma

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