Abstract 4976: Small RNA sequencing of preoperative blood plasma identifies microRNA signature enabling to find pancreatic cancer patients who will not benefit from surgical resection
Authors: Gablo Natalia , Prochazka Vladimir , Machackova Tana , Vencovska Eva , Kala Zdenek , Sana Jiri , Ahmad Parwez , Juracek Jaroslav , Vecera Marek , Svoboda Marek , Slaby Ondrej 
Published: August 2018

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer, associated with limited treatment options and high mortality rates. Radical resection remains the most effective curative approach for patients in early stage of disease. However, there is a high risk of surgical morbidity/mortality, and therefore development of prognostic assays to identify those patients who will not benefit from surgical resection, present important unmet medical need. miRNAs are small, non-coding RNAs, that post-transcriptionally regulate gene expression. miRNAs are frequently deregulated under pathological conditions including PDAC and therefore present promising candidates for new prognostic biomarkers in PDAC.

Materials and methods: We analyzed preoperative plasma samples obtained from 45 PDAC patients who underwent radical tumor resection. Patients were divided into two prognostic groups: 23 patients with poor prognosis (median overall survival (OS) = 10 months) and 22 patients with good prognosis (median OS = 25 months). cDNA libraries were prepared using CleanTaq Small RNA Library Prep Kit (TriLink). The sequencing analysis were performed by Next 500/550 High Output v2 Kit - 75 cycles using the NextSeq 500 instrument (both Illumina). For miRNA mapping and analysis, an online tool Chimira was used. Obtained data were statistically evaluated using the Bioconductor edgeR and DESeq2 package.

Results: When miRNA expression profiles of the patients from good and poor prognostic group were compared, 41 miRNAs were identified to have significantly different plasma levels between the two groups (P&lt;0.05). Out of these miRNAs, 33 were found to have significantly higher levels in plasma samples of patients with poor prognosis (e.g. mir-376a-3p, mir-6763-5p, mir-885-3p, mir-1258, mir-192-5p, mir-6751-5p, mir-891a-5p, mir-3178, mir-3173-3p, mir-378g, mir-4453, mir-6764-5p, mir-556-5p, mir-6836-5p, mir-6516-5p), and 8 miRNAs have lower levels (mir-885-3p, mir-192-5p, mir-3178, mir-8072, mir-378d, mir-99a-5p, mir-30a-5p, mir-1976) compared to those with good prognosis.

Conclusion: Our findings suggest, that there is a blood plasma miRNAs signature associated with the prognosis of PDAC patients, and after independent validation, miRNAs from this signature may allow for a prognostic stratification of PDAC patients. This work was supported by Ministry of Health of the Czech Republic, grant nr.15-33158A, 15-34553A, 15-31627A, 15-34678A, 16-31314A, 16-31765A and by grant of Czech Grant Agency nr. 16-18257S.

Citation Format: Natalia Gablo, Vladimir Prochazka, Tana Machackova, Eva Vencovska, Zdenek Kala, Jiri Sana, Parwez Ahmad, Jaroslav Juracek, Marek Vecera, Marek Svoboda, Ondrej Slaby. Small RNA sequencing of preoperative blood plasma identifies microRNA signature enabling to find pancreatic cancer patients who will not benefit from surgical resection [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 4976.