Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients.
BACKGROUND
Ovarian cancer, the leading cause of gynecologic cancer deaths, is usually diagnosed in advanced stages. Prognosis relates to stage at diagnosis and sensitivity to platinum based chemotherapy. We aimed to assess the expression of microRNAs in ovarian tumors and identify microRNA expression patterns that are associated with outcome, response to chemotherapy and survival.


METHODS
Patients, who were surgically treated for ovarian cancer between January 2000 and December 2004 were identified. Patient charts were reviewed for clinicopathologic information, follow-up and survival. Total RNA was extracted from tumor samples and microRNA expression levels were measured by microarrays. Expression levels were compared between groups of samples and statistically analyzed.


RESULTS
Fifty-seven patients were identified to fit study criteria. Of them, 19 patients had stage I disease at diagnosis, and 38 patients, stage III. All patients received platinum based chemotherapy as first line treatment. 18 microRNAs were differentially expressed (p<0.05) between stage I and stage III disease. Seven microRNAs were found to be significantly differentially expressed in tumors from platinum-sensitive vs. platinum-resistant patients (p<0.05). Five microRNAs were associated with significant differences (p<0.05) in survival or recurrence-free survival. High expression of hsa-mir-27a identified a sub-group of patients with very poor prognosis.


CONCLUSIONS
We have found an array of tumor specific markers that are associated with response to platinum based first line chemotherapy. Expression of some of these miRNAs also correlated closely with prognosis. This approach can potentially be used to tailor chemotherapy and further management to specific patient needs.
Eitan
Ram
R
The Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel. eitanr@clalit.org.il
Kushnir
Michal
M
Lithwick-Yanai
Gila
G
David
Miriam Ben
MB
Hoshen
Moshe
M
Glezerman
Marek
M
Hod
Moshe
M
Sabah
Gad
G
Rosenwald
Shai
S
Levavi
Hanoch
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
D035683:MicroRNAs; D009944:Organoplatinum Compounds