title: The significance of glypican-3 expression profiling in the tumor cellular origin theoretical system for hepatocellular carcinoma progression.
abstract: OBJECTIVE
  Glypican-3 (GPC3) expression is correlated with poor prognosis and progression in hepatocellular carcinoma (HCC). HCC progression can be associated with the differentiation status of tumor cell before malignant transformation. Our aim was to investigate the dynamic expression of GPC3 during tumor cells differentiation and to explore the role and theoretical significance of GPC3 in malignant essence of HCC.
  
  
  METHODS
  The expressions of tissue GPC3 and alpha fetoprotein (AFP) were detected by immunohistochemical staining. The tumor size, lymph node involvement, and metastasis were determined by pathological and imaging studies. HepG2 cells were induced to differentiate by all-trans retinoic acid (ATRA). Differentiation was evaluated by cytokeratin 19, gamma glutamyl transferase, and AFP through reverse transcription-polymerase chain reaction and real-time polymerase chain reaction. GPC3 staining was analyzed through flow cytometry.
  
  
  RESULTS
  Based on the immunohistochemical staining, the enrolled 316 cases were divided into two subtypes, namely, GPC3+ HCC and GPC3- HCC. Significant differences in morphology, histology variations, AFP expression, TNM staging, and overall survival curves were observed between two subtypes. During HCC differentiation induced by ATRA, the mean value of GPC3 expression treated with ATRA was much lower than the ones in placebo. There were significant differences between GPC3+ HCC and GPC3- HCC for cumulative intrahepatic and extrahepatic recurrence in early stage HCC (P = 0.009, P = 0.010).
  
  
  CONCLUSIONS
  Glypican-3 is correlated with the clinical malignant behavior of HCC. Moreover, GPC3 phenotype changes from positive to negative during tumor cells differentiation. Meanwhile, GPC3 plays a significant role in tumor cellular origin theoretical system, which can better reflect the malignant essence of tumors.
authors.affiliation: Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Xue
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Fudong
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Yueke
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Critical Care Medicine of Liver Disease, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yu
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Chenzhao
authors.initials: C
authors.lastname: Song
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Feng
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Che
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jing
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D053673:Glypicans / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D059467:Transcriptome / Q000235:genetics*; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: D053673:Glypicans; D000509:alpha-Fetoproteins
keywords: differentiation; glypican-3; hepatocellular carcinoma; heterogeneity