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Updated: May 12, 2025
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in
Satoshi Nishiwada1,2, Kota Nakamura1, Naoki Ozu3
1Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
Background:
Complete oncological local control is essential for a potential cure in patients with pancreatic ductal adenocarcinoma (PDAC), but predicting local recurrence following curative surgery remains clinically challenging. In this study, we performed comprehensive biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) following curative surgery in patients with PDAC.
Methods:
To identify axon guidance-related microRNAs, we performed the pathway-miRNA interaction analysis using the miRPathDB2.0. Subsequently, the predictive performance of the miRNAs was trained and validated in three independent clinical surgically resected sample cohorts and one pretreatment blood sample cohort with different disease statuses [upfront surgery cohort: n = 162 (training: n = 103, internal validation: n = 59), neoadjuvant chemoradiotherapy (NACRT) cohort: n = 217, arterial invasion cohort: n = 62, pretreatment blood sample cohort: n = 53].
Results:
The pathway-miRNA interaction analysis identified 13 miRNAs related to axon guidance pathway. Subsequently, we trained a 13-miRNA risk-prediction model, AGMP, which robustly distinguished PPR after surgery in the training cohort (AUC = 0.95). The AGMP was successfully validated in three independent cohorts (AUC: validation = 0.94, NACRT = 0.94, Arterial invasion = 0.90). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort, which again confirmed the robustness of risk-stratification for PPR (AUC = 0.86).
Conclusions:
We developed a novel biomarker, AGMP that demonstrated remarkable predictive performance for PPR following curative surgery in patients with PDAC; highlighting the clinical importance of the nerve-cancer cross-talk and the hopefulness as a guidepost for designing future clinical and basic research to establish individualized treatment strategies.
