Angiogenesis-related gene expression profile with independent prognostic value in advanced ovarian carcinoma.
BACKGROUND
Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients.


RESULTS
RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001).


CONCLUSIONS
It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.
Mendiola
Marta
M
Department of Pathology, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain.
Barriuso
Jorge
J
Redondo
Andrés
A
Mariño-Enríquez
Adrián
A
Madero
Rosario
R
Espinosa
Enrique
E
Vara
Juan Angel Fresno
JA
Sánchez-Navarro
Iker
I
Hernández-Cortes
Ginés
G
Zamora
Pilar
P
Pérez-Fernández
Elia
E
Miguel-Martín
María
M
Suárez
Asunción
A
Palacios
José
J
González-Barón
Manuel
M
Hardisson
David
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D012313:RNA / Q000378:metabolism
D012313:RNA