title: Hepatoma-derived growth factor: a novel prognostic biomarker in intrahepatic cholangiocarcinoma.
abstract: Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8 % (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC.
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China, guosensdu2014@163.com.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.forename: Hong-da
authors.initials: HD
authors.lastname: Liu
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Cui
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor