title: STC2 overexpression mediated by HMGA2 is a biomarker for aggressiveness of high-grade serous ovarian cancer.
abstract: High-grade serous cancer (HGSC) is a lethal form of ovarian cancer due to invasion and early metastasis. Gain of epithelial-mesenchymal transition (EMT) contributes to the aggressiveness of HGSC. High-mobility gene group A2 (HMGA2), an architectural transcription factor, plays a major role in HGSC through the regulation of EMT gene expression. Based on the gene profiling analysis, we found that the potent EMT gene, stanniocalcin 2 (STC2), was highly correlated with HMGA2 expression. In the present study, we demonstrated that STC2 was directly regulated by HMGA2 at the transcriptional level. Overexpressing STC2 in vitro directly enhanced cell migration and invasion. To investigate the correlation of STC2 and HMGA2 expression and the potential biomarker for ovarian cancer, three independent large cohorts of ovarian cancer (cohort 1=278, cohort 2=150 and cohort 3=95 cases) were examined in the present study. The results showed that the expression of HMGA2 and STC2 was positively correlated. Furthermore, STC2 expression was significantly associated with tumor grade and histotype. HGSC had significantly higher levels of STC2 expression and was inversely correlated with patient survival. These findings suggested that STC2 is an important new biomarker that can be used for HGSC.
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
authors.affiliation: Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Northwestern University School of Medicine, Chicago, IL 60611, USA.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D025743:HMGA2 Protein; D036341:Intercellular Signaling Peptides and Proteins; C114997:STC2 protein, human