title: Elevated expression of Cripto-1 correlates with poor prognosis in hepatocellular carcinoma.
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.
authors.affiliation: Department 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.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Ultrasonics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Guo
authors.affiliation: Department 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.
authors.forename: Cheng-Zuo
authors.initials: CZ
authors.lastname: Xiao
authors.affiliation: Department 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.
authors.forename: Yong-Fa
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department 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.
authors.forename: Pei-En
authors.initials: PE
authors.lastname: Jian
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Department 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department 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.
authors.forename: Rong-Ping
authors.initials: RP
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D000509:alpha-Fetoproteins / Q000032:analysis / Q000096:biosynthesis
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; D000509:alpha-Fetoproteins; D020780:Matrix Metalloproteinase 9
keywords: Cripto-1; MMP-9; aggressiveness; hepatocellular carcinoma; prognosis