International Poster Session 5 (JDDW)
November 5, 14:00–14:48, Room 16 (Kobe International Exhibition Hall No.3 Building Digital Poster Venue)
IP-26_S

Establishment of squamous molecular subtypes specific miRNA panel and validation as a non-invasive biomarker for prognostic risk stratification in patients with pancreatic ductal adenocarcinoma

Tadanobu Shimura1,2
Co-authors: Raju Kandimalla2, Saurav Mallik3, Susan Tsai4, Yoshinaga Okugawa5, Takahito Kitajima1, Hiroki Imaoka1, Mikio Kawamura1, Hiromi Yasuda1, Hiroyuki Fujikawa1, Takeshi Yokoe1, Yoshiki Okita1, Masaki Ohi1, Daisuke Izumi2, Fuminori Sonohara2, Hideo Baba6, Yasuhiro Kodera7, Yuji Toiyama1, Ajay Goel2
1
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine
2
Center for Gastrointestinal Research, Baylor Scott & White Research Institute, Baylor University Medical Center
3
Division of Biostatistics and Bioinformatics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
4
Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin
5
Department of Genomic Medicine, Mie University
6
Department of Gastroenterological Surgery, Graduate School of Medical Sciences Kumamoto University
7
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine
Background: Although recent transcriptional profiling effort in pancreatic ductal adenocarcinoma (PDAC) has led to the identification of poor prognostic molecular subtypes, their clinical translation has been challenging. Methods: By performing a systematic analysis in TCGA and ICGC cohorts, we discovered squamous poor prognostic subtype specific miRNA panel in PDAC. Subsequently, we developed models for risk stratification and investigated survival prediction probability of this panel in multiple clinical cohorts including a tissue cohort (n=199) and a preoperative serum cohort (n=51).Results: We identified squamous molecular subtypes specific 9 miRNAs (miR-205-5p, -934, -192-5p, -194-5p, -194-3p, -215-5p, -375-3p, -552-3p, and -1251-5p) with an AUC of 0.90. The validation of this panel in a tissue cohort was a significant predictor of overall survival [hazard ratio (HR): 2.48, P＜0.0001]. Moreover, we were able to successfully translate this panel into a liquid biopsy-based assay in preoperative serum specimens (HR: 2.85, P=0.02).Conclusion: We demonstrate a novel miRNA risk-stratification panel in patients with PDAC.
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