Gene expression profiles predict early relapse in ovarian cancer after platinum-paclitaxel chemotherapy.
OBJECTIVE
Women with advanced epithelial ovarian cancer are routinely treated with platinum-paclitaxel chemotherapy following cytoreductive surgery, yet only approximately 20% achieve long-term disease-free survival. We hypothesized that differences in gene expression before treatment could distinguish patients with short versus long time to recurrence after administration of platinum-paclitaxel combination chemotherapy.


METHODS
To test this hypothesis, gene expression profiling of 79 primary surgically resected tumors from women with advanced-stage, high-grade epithelial ovarian cancer was done using cDNA microarrays containing 30,721 genes. Supervised learning algorithms were applied in an effort to develop a binary classifier that could discriminate women at risk for early (< or =21 months) versus late (>21 months) relapse after initial chemotherapy.


RESULTS
A 14-gene predictive model was developed using a set of training samples (n = 51) and subsequently tested using an independent set of test samples (n = 28). This model correctly predicted the outcome of 24 of the 28 test samples (86% accuracy) with 95% positive predictive value for early relapse.


CONCLUSIONS
Predictive markers for early recurrence can be identified for platinum-paclitaxel combination chemotherapy in primary ovarian carcinoma. The proposed 14-gene model requires further validation.
Hartmann
Lynn C
LC
Mayo Clinic Cancer Center, 200 First Street Southwest, Rochester, MN 55905, USA. hartmann.lynn@mayo.edu
Lu
Karen H
KH
Linette
Gerald P
GP
Cliby
William A
WA
Kalli
Kimberly R
KR
Gershenson
David
D
Bast
Robert C
RC
Stec
James
J
Iartchouk
Natalia
N
Smith
David I
DI
Ross
Jeffrey S
JS
Hoersch
Sebastian
S
Shridhar
Viji
V
Lillie
James
J
Kaufmann
Scott H
SH
Clark
Edwin A
EA
Damokosh
Andrew I
AI
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 / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010984:Platinum / Q000008:administration & dosage; D015996:Survival Rate
D014408:Biomarkers, Tumor; D010984:Platinum; D017239:Paclitaxel