A pilot study of miRNA expression profile in surgically resected pancreatic ductal adenocarcinoma: Initial report from a bi-institutional cohort.

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies: novel therapeutic approaches beyond conventional chemotherapy are still lacking and prognosis remains poor, even for resectable patients (pts). Furthermore, there is an almost complete absence of validated predictive factors. Consequently, robust biomarkers for the early diagnosis and the prognostic stratification are urgently needed in clinical practice, especially in the context of neoadjuvant and adjuvant settings. In the last years, evidence revealed the crucial role of miRNAs in cancer initiation and progression, as well as in the chemo-resistance mechanisms, suggesting their use as clinical biomarkers. Material and methods: In this pilot study, we performed a microarray analysis to characterize global miRNA expression profile from surgical tissue samples collected from 20 resected PDAC pts pooled into 4 groups according to different clinico-pathological features: nodal metastases (N+/N-) and tumor grading (G2/G3). Results: According to expression patterns, we identified, among 384 miRNAs, a significant different modulation for 11 miRNAs associated to G2 vs G3 and for 7 miRNAs in N+ vs N- disease, suggesting a possible specific signature reflecting histological grade and nodal metastasis occurrence, respectively. We focused on 2 up-regulated (miR-138-5p and miR-518-3p) and 3 down-regulated (miR-215-5p, miR-519a-3p and miR-576-5p) miRNAs in N+ pts, and on 3 up-regulated (miR-1-3p, miR-31-5p and miR-205-5p) in G3 pts, in order to verify their possible implication in the molecular changes behind tumor differentiation and spread, as well as their potential use for prognostic and therapeutic purpose. A bio-informatic analysis was also performed, using different in silico tools, to study both high affinity miRNA targets and cross-regulated pathways among the upand down-regulated miRNAs. The results identified several associated targets involved in multiple signaling pathways commonly dysregulated in cancer. Finally, BRCA1/2 and RB1 miRNAs-mediated-modulation is actually ongoing, considering the pivotal role of these genes in some PDAC pts. Conclusion: These preliminary data provide a strong rationale to further investigate miRNAs expression in larger cohorts of PDAC pts, possibly integrating validated tissue miRNAs data with circulating miRNAs, in order to identify strong (and easily accessible) potential biomarker(s) with prognostic and/or predictive significance. Citation Format: Luca Pompella, Michela Falco, Carlo Caputo, Anna Grimaldi, Giuseppe Tirino, Severo Campione, Francesca Sparano, Maria Lucia Iacovino, Chiara Carmen Miceli, Carlo Molino, Marco Montella, Renato Franco, Gennaro Galizia, Giovanni Conzo, Vincenzo Napolitano, Annamaria Auricchio, Francesca Cardella, Fortunato Ciardiello, Michele Caraglia, Angela Lombardi, Gabriella Misso, Ferdinando De Vita. A pilot study of miRNA expression profile in surgically resected pancreatic ductal adenocarcinoma: Initial report from a bi-institutional cohort [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-052.