A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2.
Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissected serous ovarian tumors. Independent evaluation confirmed the association of a prognostic gene microfibril-associated glycoprotein 2 (MAGP2) with poor prognosis, whereas in vitro mechanistic analyses demonstrated its ability to prolong tumor cell survival and stimulate endothelial cell motility and survival via the alpha(V)beta(3) integrin receptor. Increased MAGP2 expression correlated with microvessel density suggesting a proangiogenic role in vivo. Thus, MAGP2 may serve as a survival-associated target.
Mok
Samuel C
SC
Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Bonome
Tomas
T
Vathipadiekal
Vinod
V
Bell
Aaron
A
Johnson
Michael E
ME
Wong
Kwong-kwok
KK
Park
Dong-Choon
DC
Hao
Ke
K
Yip
Daniel K P
DK
Donninger
Howard
H
Ozbun
Laurent
L
Samimi
Goli
G
Brady
John
J
Randonovich
Mike
M
Pise-Masison
Cindy A
CA
Barrett
J Carl
JC
Wong
Wing H
WH
Welch
William R
WR
Berkowitz
Ross S
RS
Birrer
Michael J
MJ
D002448:Cell Adhesion; D002465:Cell Movement; D003285:Contractile Proteins / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis
D003285:Contractile Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C115627:MFAP5 protein, human; D011994:Recombinant Proteins