Intrahepatic Recurrence After Curative Resection of Hepatocellular Carcinoma

Poon, Ronnie Tung‐Ping; Fan, Sheung‐Tat; Lo, Chung‐Mau; Liu, Chi‐Leung; Wong, John

doi:10.1097/00000658-199902000-00009

Cited by 533 publications

(458 citation statements)

References 29 publications

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“…As vascular invasion frequently occurs in HCC and often predicts tumor invasion and metastasis (Poon et al, 1999), our finding may be interpreted as PFTK1 overexpressions that correlate with a more aggressive tumor phenotype. We also obtained functional evidence showing the mechanistic action of PFTK1 protein kinase through an intermediate substrate TAGLN2.…”

Section: Discussionmentioning

confidence: 67%

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

et al. 2011

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The PFTK1 gene encodes a cdc2-related serine/threonine protein kinase that has been shown to confer cell migratory properties in hepatocellular carcinoma (HCC). However, the prognostic value and biological mechanism by which PFTK1 promotes HCC motility remain largely unknown. Here, we showed from tissue microarray that common upregulations of PFTK1 in primary HCC tumors (n ¼ 133/180) correlated significantly with early age onset (p40 years), advance tumor grading and presence of microvascular invasion (Pp0.05). To understand downstream phosphorylated substrate(s) of PFTK1, phospho-proteins in PFTK1 expressing and knockdown Hep3B cells were profiled by two-dimensional-polyacrylamide gel electrophoresis mass spectrometric analysis. Protein identification of differential spots revealed b-actin (ACTB) and transgelin2 (TAGLN2) as the two most profound phosphorylated changes affected by PFTK1. We verified the presence of TAGLN2 serine phosphorylation and ACTB tyrosine phosphorylation. Moreover, reduced TAGLN2 and ACTB phosphorylations in PFTK1-suppressed Hep3B corresponded to distinct actin depolymerizations and marked inhibition on cell invasion and motility. Given that TAGLN2 is a tumor suppressor whose function has been ascribed in cancer metastasis, we examined if TAGLN2 is an intermediate substrate in the biological path of PFTK1. We showed in PFTK1-suppressed cells that knockdown of TAGLN2 over-rode the inhibitory effect on cell invasion and motility, and a recovery on actin polymerization was evident. Interestingly, we also found that unphosphorylated TAGLN2 in PFTK1-suppressed cells elicited strong actin-binding ability, a mechanism that possibly halts the actin cytoskeleton dynamics. Site-directed mutagenesis of TAGLN2 suggested that PFTK1 regulates the actinbinding affinity of TAGLN2 through the S83 and S163 residues, which if mutated can significantly affect HCC cell motility. Taken together, our data propose a novel, oncogene-tumor suppressor interplay, where oncogenic PFTK1 confers HCC cell motility through inactivating the actin-binding motile suppressing function of TAGLN2 via phosphorylation.

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Section: Discussionmentioning

confidence: 67%

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

et al. 2011

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“…26 Portal vein thrombosis had been found to be a poor prognostic variable in multiple studies. 27 Microscopic and macroscopic portal vein involvement is one of the major modes of spread of HCC, leading to recurrence after resection 28 and transplantation. 29 In addition, portal venous thrombosis can lead to complications of portal hypertension such as ascites, variceal hemorrhage, and worsening hepatic function in HCC patients.…”

Section: Discussionmentioning

confidence: 99%

Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort

et al. 2005

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Currently there is no consensus which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1-and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P ‫؍‬ .001), portal vein thrombosis (P ‫؍‬ .0001), and tumor diameter greater than 4 cm (P ‫؍‬ .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC. ( H epatocellular carcinoma (HCC) is the fifth most common tumor worldwide. In the United States, the incidence of HCC has been rising, 1 and it is the tumor with the largest increase in incidence over the last 12 years. 2 Furthermore, the overall survival of patients with HCC has not improved over the last 20 years, with the incidence rate almost equal to the death rate. 3 It is projected that the increase in incidence of HCC will continue over the next 20 years in the United States. 4 Therefore, it is important to understand the factors that predict survival of patients with HCC.

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“…Despite several individual small trials that have demonstrated potential benefit of some adjuvant therapies, evidence from such trials is weak and there is no well-proven effective adjuvant treatment to prevent recurrence so far [263]. Aggressive management of tumor recurrence by repeat resection, ablation, or transarterial chemoembolization (TACE) is currently the most practical way to prolong patient survival [263,264].…”

Section: Liver Resectionmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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Introduction The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. 123Hepatol Int (2010) 4: 439-474 DOI 10.1007/s12072-010-9165-7 Results Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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Intrahepatic Recurrence After Curative Resection of Hepatocellular Carcinoma

Cited by 533 publications

References 29 publications

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

A novel interplay between oncogenic PFTK1 protein kinase and tumor suppressor TAGLN2 in the control of liver cancer cell motility

Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

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