SERPINB3 is associated with TGF-β1 and cytoplasmic β-catenin expression in hepatocellular carcinomas with poor prognosis

Turato, Cristian; Vitale, Alessandro; Fasolato, S.; Ruvoletto, Mariagrazia; Terrin, Liliana; Quarta, Santina; Morales, R. Ramirez; Biasiolo, Alessandra; Zanus, Giacomo; Zali, Narges; Tan, Poh Seng; Hoshida, Yujin; Gatta, Angelo; Cillo, Umberto; Pontisso, Patrizia

doi:10.1038/bjc.2014.246

Cited by 62 publications

(96 citation statements)

References 55 publications

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“…Recent studies indicate that SerpinB3 is up-regulated by oncogenic Ras, promotes NF-kB-related inflammatory cytokine production 30 and induces IL-6 autocrine signaling 31 , favouring tumour progression. These findings are in keeping with the reported high levels of SerpinB3 detected in the sub-class of HCCs with poor prognosis 32 . A previous study from our group has shown that SerpinB3 is expressed in the majority of hepatoblastomas, where SerpinB3 levels were positively correlated with the extent of Myc expression and tumour diffusion 33 .…”

supporting

confidence: 91%

SerpinB3 and Yap interplay increases Myc oncogenic activity

Turato

Cannito

Simonato

et al. 2015

Digestive and Liver Disease

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Primary liver cancer, mainly hepatocellular carcinoma (HCC), is one of the leading causes of cancer-related death worldwide 1 and generally has a poor prognosis since it is often diagnosed at an advanced stage when treatment is not effective. Great efforts have been made to decipher the molecular mechanisms of HCC and gene expression profiling has been used to identify subgroups of patients according to etiological factors, early pre-neoplastic lesions, stage of the disease, rate of recurrence and survival [2][3][4][5] . Genetic analysis has revealed that Myc oncogene over-expression is present in up to 70% of viral and alcohol-related HCCs. Myc is a potent activator of tumorigenesis and its deregulation has been shown to contribute to a variety of cancers [6][7][8] . Increased Myc levels often correlate with the more advanced and aggressive tumour forms, providing a characteristic signature of cancer progenitor cells and suggesting that its overexpression plays some part in Myc-driven pathogenesis and tumor biology 9,10 . The Myc oncoprotein is a pleiotropic transcription factor belonging to the basic helix-loop-helix-leucine zipper family with a critical role in engaging and coordinating expression of the genes necessary for efficient and ordered proliferation of somatic cells. Myc expression is highly regulated being tightly controlled by a number of mechanisms involving many transcriptional regulatory motifs 11,12 . According to its well established predominant role Myc regulates up to 15% of human genes and is involved in cell growth, proliferation, metabolism, differentiation, and apoptosis 6 . According to data emerging from genome-wide gene expression profiling 13 Myc has been recently suggested to be at the centre of human liver tumor malignant conversion.As expected, given their broad role as transcriptional regulator, Myc family proteins are predominantly localized within nuclear compartment during proliferation, although emerging data indicate

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supporting

confidence: 91%

SerpinB3 and Yap interplay increases Myc oncogenic activity

Turato

Cannito

Simonato

et al. 2015

Digestive and Liver Disease

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“…The significant impact of SCCA-IgM determination in defining patient prognosis was confirmed also by data showing that SCCA-IgM levels and tumor size were the only identified independent predictors of overall survival [53] . Although these findings must be confirmed in further studies, they are supported by recent data demonstrating that liver tumors with high SCCA-1 tissue expression exhibit higher early recurrence after surgical resection [38] .…”

Section: Scca-igm and Antiviral Treatmentsupporting

confidence: 60%

“…Furthermore, this serpin was identified in the majority of hepatoblastomas, with the highest levels in tumours of more advanced stage [37] . In HCC, high expression of SERPINB3 is significantly associated with early tumour recurrence, and shows a better prognostic significance than other clinical and histological variables [38] . These important clinical findings were confirmed at the mole cular level: SCCA expression in liver tumor has been correlated with liver regeneration activity (expressed by MIB-I-labeling index) [39] , and increased proliferation was also documented in hepatoma cell lines overexpressing SERPINB3 and in a mouse model transgenic for this serpin [39,40] .…”

Section: Sccamentioning

confidence: 97%

Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C

Martini

Gallotta

Pontisso

et al. 2015

WJH

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Hepatitis C virus (HCV) is the main cause of chronic liver disease and cirrhosis in Western countries. Over time, the majority of cirrhotic patients develop hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide -fourth for incidence rate. A high public health priority need is the development of biomarkers to screen for liver disease progression and for early diagnosis of HCC development, particularly in the high risk population represented by HCV-positive patients with cirrhosis. Several studies have shown that serological determination of a novel biomarker, squamous cell carcinoma antigen-immunoglobulins M (SCCA-IgM), might be useful to identify patients with progressive liver disease. In the initial part of this review we summarize the main clinical studies that have investigated this new circulating biomarker on HCV-infected patients, providing evidence that in chronic hepatitis C SCCA-IgM may be used to monitor progression of liver disease, and also to assess the virological response to antiviral treatment. In the last part of this review we address other, not less important, clinical applications of this biomarker in hepatology. Core tip: A high public health priority need is the development of biomarkers to screen for liver disease progression in hepatitis C virus (HCV)-positive patients. Serological squamous cell carcinoma antigen-immunoglobulins M has shown the ability to identify patients with progressive liver disease and patients at higher risk of hepatocellular carcinoma development. In this review we summarize the main clinical studies performed using this new circulating biomarker for monitoring cirrhosis progression in HCV-positive patients and to evaluate virological response to antiviral treatment. Clinical applications of squamous cell carcinoma antigenimmunoglobulins M to monitor chronic hepatitis C Martini A, Gallotta A, Pontisso P, Fassina G. Clinical applications of squamous cell carcinoma antigen-immunoglobulins M to monitor chronic hepatitis C. MINIREVIEWS

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“…In addition a very recent study revealed that high levels of SERPINB3 were detectable in 22% of HCCs specimens from cirrhotic patients and were found to be significantly associated with early tumor recurrence, then representing a candidate prognostic marker able to identify the subset of most aggressive HCCs [51]. …”

Section: Implicated Inmentioning

confidence: 99%