John K Chan1, Tuyen K Kiet2, Kevin Blansit3, Rashmi Ramasubbaiah4, Joan F Hilton5, Daniel S Kapp6, Daniela Matei4. 1. 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. 2. 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. 3. 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. 4. 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. 5. Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, 980 W. Walnut Street, R3 C218D, Indianapolis, IN 46202, U S A. 6. Department of Radiation Oncology, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.
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.
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 humantumors 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: Weiwei Gong; Caixia Zhu; Yueyang Liu; Alexander Muckenhuber; Holger Bronger; Andreas Scorilas; Marion Kiechle; Julia Dorn; Viktor Magdolen; Tobias Dreyer Journal: Am J Transl Res Date: 2021-03-15 Impact factor: 4.060
Authors: James S Ferriss; James J Java; Michael A Bookman; Gini F Fleming; Bradley J Monk; Joan L Walker; Howard D Homesley; Jeffrey Fowler; Benjamin E Greer; Matthew P Boente; Robert A Burger Journal: Gynecol Oncol Date: 2015-07-26 Impact factor: 5.482