Background: High-grades serous carcinoma (HGSC) is the most aggressive subtype of ovary cancer. The disease appears at three anatomic sites: ovary tumor, solid metastasis and effusions. Not much is known about the regulatory pathways involved in cancer progression. Long non coding RNA (lncRNA) is non protein coding RNA with size >200bp. Exosomes are 30-100nm endosomal-derived vesicles containing mRNA, miRNA, lncRNA, transcription factors, proteins and lipids. They are secreted from various cells and their substance and amount alter between healthy and diseases state.

Objective: Identification of lncRNA effecting cancer progression and patient survival.

Methods: Custom made lncRNA microarray (composed off˜17,000 lncRNAs and˜22,000 mRNAs) followed by validation series of 180 specimens from three anatomic sites, including 77 effusions, 40 ovarian HGSC specimens, 21 solid metastases and exosomes from 42 effusion supernatants. 10 selected lncRNA were subjected to clinicopathologic parameters and survival association analysis.

Results: out of 10 lncRNA chosen for validation, 5 lncRNA- ESRG, Link-A, MEG3, GATS and PVT1 - were differently expressed between the anatomic sites and exosomes (all p<0.001). In univariate survival analysis, higher ESRG levels were significantly related to longer overall survival (OS) in the entire cohort (p=0.023), Higher Link-A levels in post-chemotherapy specimens was significantly associated with longer OS (p=0.015). MEG3 levels were significantly higher in pre-chemotherapy effusions tapped at diagnosis (n=40) compared to post-chemotherapy specimens (p=37; p=0.017). Higher GATS expression was seen in specimens from patients who were sub-optimally debulked (p=0.046). Moreover, H19 which did not change significantly between the anatomic sites, was higher in effusions from patients whose tumors showed primary resistance to chemotherapy (PFS≤6 months).

Conclusion: lncRNAs are differently express at different anatomic site and exosomes in HGSC and can provide new therapeutic targets. Furthermore, their level in effusion fluids can serve as a prognostic marker.

Citation Format: Natalie Filippov-Levy, Yoav Smith, Claes Gøran Trope, Ben Davidson, Reuven Reich. LncRNA expression at the different site of high-grades serous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 517.