Abstract TMEM-037: GENE EXPRESSION ANALYSIS IDENTIFIES IMMUNOLOGICAL MRNA UP REGULATION IN CELLS IN THE ASCITES OF SEROUS OVARIAN CANCER AS COMPARED TO MATCHED PRIMARY TUMOR
Authors: Robertson Sharon E. , Marchion Douglas C. , Xiong Yin , Berglund Anders E. , Magliocco Anthony M. 
Published: June 2017

BACKGROUND: Ovarian cancer patients with advanced disease frequently develop ascites. It is currently unclear to what extent the molecular phenotype of the cells in ascites differs from that of the primary ovarian tumor. There is also speculation that the tumor cells in ascites may represent a more treatment resistant cell population. An improved understanding of the biology of the cellular environment in ovarian cancer-related ascites may reveal opportunities to develop new targeted therapies that may not be apparent through analysis of the primary tumor alone. The aim of the study was to evaluate potential biological differences between the cellular environment of primary ovarian tumors and that of the ascites fluid.

METHODS: We performed mRNA expression in n=12 matched pairs of primary serous OVCA tumor and the cellular component of ascites using the HTG Edge System and the EdgeSeq Oncology Biomarker Panel assay. After normalization, log expression values for 2650 genes were compared between tumor and ascites samples using principle component analysis (PCA) modeling. The molecular profiles of primary tumor and ascites were compared using a t-test. Additionally, the CiberSort algorithm was applied to estimate the relative composition of tumor infiltrating lymphocytes in tumor and ascites samples.

RESULTS: PCA modeling demonstrated a clear difference between the primary tumor and ascites samples using all genes. A group comparison (q&lt;0.01, FDR corrected p-value, fold change &gt;2) indicated that 49 genes were differentially expressed between primary tumor and ascites samples. Ascites samples showed significantly higher expression of T-cell markers, CD2, CD3D, CD4, and CD8A, as well as the monocyte/macrophage markers CD14, CCL4, CD163, CCR1, IL10, and ITGAM. CiberSort analysis revealed a high proportion of eosinophils (p &lt;2 x 10^-7) and monocytes (p&lt;0.0002) in ascites as compared to tumor while resting mast cells were proportionately greater in the tumor samples (p &lt; 4 x 10^-5).

CONCLUSIONS: In this study, we report a significant difference in mRNA expression between primary tumors from serous OVCA and ascites. Ascites samples were found to have higher expression of T cell, monocyte and macrophage mRNA. Interestingly, ascites samples also expressed an increased proportion of eosinophils as compared to primary tumor. Eosinophils have been suggested to be essential for CD8+ T-cell mediated tumor rejection and have been associated with improved outcomes in prognosis. We also report an increased proportion of resting mast cells in primary tumor. Mast cells are increasingly thought to play a role in the regulation of tumor growth. In summary, this study demonstrates that molecular profile of cells in ascites is different than that of primary tumor and that this difference is potentially due to immune modulators.

Citation Format: Sharon E. Robertson, MD, MPH, Douglas C. Marchion, PhD, Yin Xiong, PhD, Anders E. Berglund, PhD, Anthony M. Magliocco, MD. GENE EXPRESSION ANALYSIS IDENTIFIES IMMUNOLOGICAL MRNA UP REGULATION IN CELLS IN THE ASCITES OF SEROUS OVARIAN CANCER AS COMPARED TO MATCHED PRIMARY TUMOR [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-037.