Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence

Ying Hong Shi, Wen Xing Ding, Jian Zhou, Jun Yi He, Yang Xu, Andrea A. Gambotto, Hannah Rabinowich, Jia Fan, Xiao-Ming Yin

Research output: Contribution to journalArticle

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long-term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fiAly understood. Our initial studies in established HCC cell lines with different metastatic capabilities indicated a correlation of metastasis with the resistance to apoptosis and therefore the ability to survive in stressed conditions. Subsequent investigation revealed that increased expression of X-linked inhibitor-of-apoptosis protein (XIAP) was correlated with the resistance to apoptosis and enhanced invasiveness in vitro, which could contribute to increased metastatic foci in vivo. Furthermore, we found that nearly 90% of clinical samples from advanced HCC patients expressed high levels of XIAP. Patients with XIAP-positive tumors had a significantly increased risk of relapse, which resulted from metastasis after total liver resection and orthotopic liver transplantation. Indeed, XIAP expression could be an independent prognostic factor for predicting disease-free survival rate and overall survival rate of these patients. XIAP expression was also highly correlated with advanced cases that exceeded the Milan criteria and could be a prognostic factor for disease-free survival in these patients as well. Conclusion: Our studies have shown an important molecule in controlling HCC metastasis, defined a biomarker that can be used to predict HCC recurrence and patient survival after treatment, and suggest that XIAP can be a molecular target subject to intervention to reduce metastasis and recurrence.

Original languageEnglish (US)
Pages (from-to)497-507
Number of pages11
JournalHepatology
Volume48
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

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X-Linked Inhibitor of Apoptosis Protein
Hepatocellular Carcinoma
Neoplasm Metastasis
Recurrence
Neoplasms
Disease-Free Survival
Survival Rate
Apoptosis
Therapeutic Uses
Liver Transplantation
Biomarkers
Cell Line
Survival
Liver
Therapeutics

ASJC Scopus subject areas

  • Hepatology

Cite this

Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence. / Shi, Ying Hong; Ding, Wen Xing; Zhou, Jian; He, Jun Yi; Xu, Yang; Gambotto, Andrea A.; Rabinowich, Hannah; Fan, Jia; Yin, Xiao-Ming.

In: Hepatology, Vol. 48, No. 2, 08.2008, p. 497-507.

Research output: Contribution to journalArticle

Shi, YH, Ding, WX, Zhou, J, He, JY, Xu, Y, Gambotto, AA, Rabinowich, H, Fan, J & Yin, X-M 2008, 'Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence', Hepatology, vol. 48, no. 2, pp. 497-507. https://doi.org/10.1002/hep.22393
Shi, Ying Hong ; Ding, Wen Xing ; Zhou, Jian ; He, Jun Yi ; Xu, Yang ; Gambotto, Andrea A. ; Rabinowich, Hannah ; Fan, Jia ; Yin, Xiao-Ming. / Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence. In: Hepatology. 2008 ; Vol. 48, No. 2. pp. 497-507.
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