title: MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer.
abstract: OBJECTIVE
  To determine the role of miR-378 as a biomarker for anti-angiogenic therapy response in ovarian cancer.
  
  
  METHODS
  Expression of miR-378 was analyzed in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were identified using microarray. Data from The Cancer Genome Atlas (TCGA) was utilized to correlate miR-378 expression with progression-free survival (PFS) among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox proportional hazards.
  
  
  RESULTS
  MiR-378 was overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian cancer cells altered expression of genes associated with angiogenesis (ALCAM, EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70, LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated with longer PFS in a subset of patients with recurrent ovarian cancer treated with bevacizumab (9.2 vs. 4.2months; p=0.04). On multivariate analysis, miR-378 expression was an independent predictor for PFS after anti-angiogenic treatment (HR=2.04, 95% CI: 1.12-3.72; p=0.02). Furthermore, expression levels of two miR-378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of patients who received anti-angiogenic therapy (9.4 vs. 4.2months, p=0.04 for high vs. low ALCAM; 7.9 vs. 2.3months, p<0.01 for low vs. high EHD1).
  
  
  CONCLUSIONS
  Our data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs. normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as markers for response to anti-angiogenic therapy.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco School of Medicine, 1600 Divisadero Street, Box 1702, San Francisco, CA 94143, USA; Palo Alto Medical Foundation Research Institute, 795 El Camino Real, Palo Alto, CA 94301, USA. Electronic address: chanjohn@obgyn.ucsf.edu.
authors.forename: John K
authors.initials: JK
authors.lastname: Chan
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco School of Medicine, 1600 Divisadero Street, Box 1702, San Francisco, CA 94143, USA.
authors.forename: Tuyen K
authors.initials: TK
authors.lastname: Kiet
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco School of Medicine, 1600 Divisadero Street, Box 1702, San Francisco, CA 94143, USA; Palo Alto Medical Foundation Research Institute, 795 El Camino Real, Palo Alto, CA 94301, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Blansit
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco School of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 185 Berry Street, Box 0560, San Francisco, CA 94143, U S A.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Ramasubbaiah
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, 980 W. Walnut Street, R3 C218D, Indianapolis, IN 46202, U S A.
authors.forename: Joan F
authors.initials: JF
authors.lastname: Hilton
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kapp
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco School of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 185 Berry Street, Box 0560, San Francisco, CA 94143, U S A.
authors.forename: Daniela
authors.initials: D
authors.lastname: Matei
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D000068258:Bevacizumab
keywords: Anti-angiogenic therapy; MiR-378; MicroRNA; Ovarian cancer; Survival