title: Overexpression of Dickkopf-1 predicts poor prognosis for patients with hepatocellular carcinoma after orthotopic liver transplantation by promoting cancer metastasis and recurrence.
abstract: Our previous data had shown that Dickkopf-1 (DKK1) combined with β-catenin was a novel prognostic predictor for hepatocellular carcinoma (HCC) patients. However, the role and mechanism of DKK1 in HCC recurrence or metastasis remain poorly understand. This study was to assess the role of DKK1 in tumor metastasis for patients with hepatocellular carcinoma after orthotopic liver transplantation (OLT). The expression of DKK1 protein was detected in hepatic cell lines, HCC cell lines, and HCC patients after OLT with different potential of metastasis. After DKK1 expression in the HCCLM3 cells was downregulated by siRNA-mediated approach, the role of DKK1 in cell invasion and metastasis was investigated. cDNA genechip was used to analyze the differential expressed genes related with DKK1 in two pairs of HCC cells. The prognostic significance of DKK1 was further assessed by Kaplan-Meier and Cox regression analyses in 148 HCC patients after OLT. The expression of DKK1 protein was higher in the high-invasive HCC cells and HCC patients of the disease recurrence group. With the downregulation of DKK1, HCCLM3 cells showed decreased aggressiveness in vitro and lower metastatic ability in vivo. DKK1 could regulate many genes involved in biological processes and pathways related with tumor progression. Furthermore, DKK1 overexpression correlated with tumor microvessel density in clinical HCC samples. Multivariate analysis revealed that DKK1 was an independent prognostic indicator for overall survival and cumulative recurrence in this cohort of HCC patients post-OLT. Collectively, overexpression of DKK1 was implicated in invasion/metastasis of HCC after OLT and DKK1 overexpression may be potential molecular therapeutic targets for liver cancer.
authors.affiliation: Medical College of Nantong University, Nantong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Xinrong
authors.initials: X
authors.lastname: Yang
authors.forename: Fengbo
authors.initials: F
authors.lastname: Zhao
authors.forename: Qiujin
authors.initials: Q
authors.lastname: Shen
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiufang
authors.initials: X
authors.lastname: Lv
authors.forename: Baoying
authors.initials: B
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D034622:RNA Interference; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins