title: SOX4 is associated with poor prognosis in cholangiocarcinoma.
abstract: Overexpressions of EGFR and HER2 are thought to be prognostic factors of cholangiocarcinoma (CCA). The SOX4 transcription factor is involved in the development and cell fate decision. Although up-regulation of SOX4 has been described in multiple human malignancies, the prognostic value of SOX4 and its relationship to EGFR/HER2 in CCA remain unclear. In the current study, we showed that SOX4 and EGFR were overexpressed in 17 (29.3%), and 13 (22.4%) of the 58 intrahepatic cholangiocarcinomas (IHCCs), as well as 28 (29.8%), and 33 (35.1%) of the 94 extrahepatic cholangiocarcinomas (EHCCs), respectively. Overexpression of HER2 was exclusively identified in EHCCs, with the rate being 4.4% (4/90). In all, amplification of EGFR was identified in 1.8% (1/52) of IHCC cases, and in 2% (3/82) of EHCC cases. By contrast, HER2 amplification was present only in 3.5% (3/94) of the EHCC cases. Notably, Kaplan-Meier survival analysis suggested that SOX4 expression is a significant prognostic factor for poor prognosis in IHCC patients. Importantly, our findings suggested significant association of SOX4 and EGFR expression both in IHCC (P<0.001) and EHCC (P=0.014). SOX4 may modulate expression of EGFR, and SOX4+/EGFR+ defines a subset of CCA patients with poor prognosis. Finally, in vitro data indicated that SOX4 inhibits cellular migratory capacity and promotes epithelial-mesenchymal transition (EMT) process of CCA cells. Collectively, our results define an important role for SOX4 in CCA by orchestrating EMT and modulation on EGFR expression. SOX4 expression may serve as a prognostic marker for patients with IHCC.
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, China; Department of General Surgery, Yishui Central Hospital, Linyi, China.
authors.forename: Weishan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Shandong Provincial Hospital, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Linyi People's Hospital, Linyi, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Surgery, Jinan Central Hospital, Jinan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China.
authors.forename: Muyi
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, China; Department of Pathology, Shandong University Qilu Hospital, Jinan, China. Electronic address: boh@sdu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of General Surgery, Shandong University Qilu Hospital, Jinan, China. Electronic address: husanyuan1962@hotmail.com.
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Hu
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D055751:SOXC Transcription Factors; C083431:SOX4 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Cholangiocarcinoma; EGFR; Epithelial–mesenchymal transition; Prognosis; SOX4