Oncotarget

Clinical Research Papers:

Elevated expression of Cripto-1 correlates with poor prognosis in hepatocellular carcinoma

Jia-hong Wang _, Wei Wei, Jing Xu, Zhi-xing Guo, Cheng-zuo Xiao, Yong-fa Zhang, Pei-en Jian, Xiao-liang Wu, Ming Shi and Rong-ping Guo

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Oncotarget. 2015; 6:35116-35128. https://doi.org/10.18632/oncotarget.5057

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Abstract

Jia-hong Wang1,*, Wei Wei1,*, Jing Xu2, Zhi-xing Guo3, Cheng-zuo Xiao1, Yong-fa Zhang1, Pei-en Jian1, Xiao-liang Wu2, Ming Shi1, Rong-ping Guo1

1Department of Hepatobilliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

2State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

3Department of Ultrasonics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

*These authors have contributed equally to this work

Correspondence to:

Rong-Ping Guo, e-mail: guorp@sysucc.org.cn

Keywords: hepatocellular carcinoma, Cripto-1, MMP-9, aggressiveness, prognosis

Received: April 20, 2015     Accepted: August 24, 2015     Published: September 05, 2015

ABSTRACT

Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR). Cripto-1 expression was increased in TNM and BCLC stage-dependent manner. Cripto-1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM and BCLC stage. In addition, Cripto-1 was positively correlated with MMP-9 among 205 HCC samples. Patients with Cripto-1 upregulation had poor OS and shorter TTR in low and high aggressiveness groups. Furthermore, Cripto-1 had predictive validity for early and late recurrence in HCC patients. Combination of Cripto-1 and serum AFP was correlated with OS and TTR. In conclusion, Cripto-1 overexpression contributes to aggressiveness and poor prognosis of HCC. Cripto-1/AFP expression could be a potential prognostic biomarker for survival in HCC patients.


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