Abstract 4150: Circulating microRNA patterns in ovarian cancer increased expression with surgical intervention and chemotherapy: Stable high presurgical “survival pattern” (SP) miRNA expression may reflect intrinsic ability for recognition and elimination of malignancy
Authors: Shapira Iuliana , Lee Annette , Keogh Mary , Mason Cathleen , Oswald Michaela , Lovecchio John , Liang Sharon , Whyte Jill , Bhuiya Tawfiqul , Cheng Kit , Mekan Sabeen , Gleason Karen , John Veena , Devoe Craig , Budman Daniel 
Published: August 2012

Background: Epithelial ovarian cancer accounts for 90% of all cases of malignant tumors of the ovaries, the majority of patients are diagnosed at stage III disease with 70% of them succumbing to their disease within 5 years. Objectives: We addressed 3 questions 1) are there patterns in the pre-surgical miRNA profiles between survivors of stage III ovarian cancer and patients who do not survive the disease “surviving pattern” (SP) 2) are there changes in the miRNA profiles that occur during or after chemotherapy that convert patients into SP. 3) Do patients with benign ovarian masses have the SP? Methods: Between 2004 and 2011 we investigated in patterns of circulating miRNAs collected before, after surgery, during and after chemotherapy in patients presenting for surgery for ovarian masses. We also collected blood at ovarian cancer relapse and tumor and benign ovary (if available) for miRNA analysis. Raw Ct values obtained from Taqman and software Data Assist. Data were processed via programming language R. Raw data were normalized using the least variable miRNA from dataset. Differential expression was studied using the R/Bioconductor package “limma” using moderated t-statistic allowing both 2 sample comparison and multiple sample comparison. Only results with a p&lt;0.05 were considered statistically significant. Characteristics: Six patients were operated for benign ovarian masses; 14 patients had carcinoma. Conclusion: Two patients were long term survivors of ovarian cancer diagnosed in 2004. Both had serum miRNA SP before surgical removal of tumor and at 2011 follow up. The SP pattern was not seen in any of the non-surviving ovarian cancer patients in the pre-surgical samples, post surgical samples, samples obtained during chemotherapy or at relapse. The SP pattern was not observed in the patients operated for benign ovarian masses. During chemotherapy circulating miRNA increased between 2 to 80 fold, none decreased. Most notable increases in miRNA levels were miR-16 (80x), miR-195 (50x), miR-25 (47x), miR-19a (40x), miR-19b (42x), miR-20a (36x), miR-29c (22x), miR-222 (23x), miR-146a (21x), miR-130a (21x) and miR-223 (21x). Discussion: Malignant cells are stressed during chemotherapy and rise in miRNA levels facilitate adaptation to novelty and the speed of evolutionary process needed for survival under stressful situations. This study suggests that abrupt rise in miRNA is the conserved mechanism of evolutionary adaptation during chemotherapy stress. It also suggests that specific miRNAs (SP) deter cancer progression in certain individuals. If SP is duplicated in larger cohorts the results will have important implications for the development of “replacement” miRNA therapies of the future.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4150. doi:1538-7445.AM2012-4150