Unique gene expression profile based on pathologic response in epithelial ovarian cancer.
OBJECTIVE
We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC).


METHODS
Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients.


RESULTS
A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set, the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX, a proapoptotic protein previously associated with chemotherapy response in ovarian cancer.


CONCLUSIONS
Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway.
Spentzos
Dimitrios
D
Program of Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Levine
Douglas A
DA
Kolia
Shakirahmed
S
Otu
Hasan
H
Boyd
Jeff
J
Libermann
Towia A
TA
Cannistra
Stephen A
SA
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins