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MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival.

Background: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. Methods: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. Results: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P

Background: Black women with triple negative breast cancer have 46% lower survival rates; this may be due to differences in tumor biology. We analyzed presurgical plasma microRNA of white (W) and black (B) women with TNBC enrolled in the breast ovarian tissue bank to detect if differences in the pre-surgical plasma microRNA could be detected in B patients relative to W patients relative to healthy controls. Aims: MicroRNA in pre-surgical plasma of TNBC W or B was compared to plasma from controls race and age matched controls to assess if differences in plasma and tumor microRNA may explain the survival disparity observed in B. We addressed 2 questions 1) are the patterns in the pre-surgical miRNA profiles different between W and B patients, differences that could explain outcomes discrepancy? 2) What are the miRs changes in patients W or B relative to healthy controls? Methods: Between 2004 and 2011 plasma miRNAs was measured before, after surgery, during and after chemotherapy in 73 surgical breast cancer patients and 11 age and race matched controls. We also analized miRs in the tumor and benign adjacent breast in 5 specimes. Samples were analyzed using qRT-PCR in the ABI's TaqMan OpenArray Panel for 750 miRs. Samples were spiked with ath-miR-159a and hsa-miR-320 most strongly correlated in its expression to ath-miR-159a through the Pearson correlation coefficient. 2-sample t-test was used for comparisons between means and ANOVA followed by post-hoc test to compare the mean response between subject factors of interest. All tests were 2-tailed; statistical significance was set at p < 0.05. Results: 44 W and 23 B, mean age at surgery 48 years (range 35–78) and 11 controls – mean age 44 years (range 35–67). Black TNBC patients did not express over 70 % of pre-surgical plasma miRs present in the W pre-surgical plasma. B over-expressed high levels of miR-1244, -190 and -638, which were not detected in any of the W patients (p < 0.005). W patients and controls expressed miRs10a, -190, -502-3p, -548, and -9* not detected in B TNBC patients. White patients over-expressed over 80% of plasma miRs present in controls, while black patients over-expressed only 30% of miRs present in controls (P < 0.005). Conclusions: Patterns of pre-surgical miR expression are different in B versus W patients with TNBC. In B the presence of TNBC leads to silence in circulating plasma miRs in comparison to W and controls. In W the presence of the tumor increases the miR “chatter”. Black patients have a different “communication” style between host-TNBC when analyzed by the response of plasma microRNA. This difference may call for different treatment protocols for patients. Specific treatment interventions, such as administration of chemotherapy before surgery, in an attempt to increase the microRNA levels in plasma may improve the outcomes of black patients with TNBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-13.

e16557 Background: It is estimated that over 20,000 new cases of ovarian cancer are diagnosed annually. The workup of ovarian mass and diagnosis of cancer present a significant challenge on both pa...

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 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