Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep;60(9):1174-1189.
doi: 10.1007/s00535-025-02260-w. Epub 2025 May 10.

An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in patients with pancreatic cancer

Satoshi Nishiwada  1   2 , Kota Nakamura  1 , Naoki Ozu  3 , Taichi Terai  1 , Yuichiro Kohara  1 , Minako Nagai  1 , Takeshi Sakata  1 , Shunsuke Doi  1 , Yasuko Matsuo  1 , Satoshi Yasuda  1 , Toshihiro Tanaka  4 , Masayuki Sho  5
Affiliations

An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in patients with pancreatic cancer

Satoshi Nishiwada et al. J Gastroenterol. 2025 Sep.

Abstract

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.

Keywords: Axon guidance-related miRNAs; Liquid biopsy biomarker; Pancreatic cancer; Perivascular plexus local recurrence.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: None.

References

    1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. - PubMed
    1. Groot VP, Gemenetzis G, Blair AB, et al. Defining and predicting early recurrence in 957 patients with resected pancreatic ductal adenocarcinoma. Ann Surg. 2019;269(6):1154–62. - PubMed
    1. Groot VP, Rezaee N, Wu W, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267(5):936–45. - PubMed
    1. Ishido K, Hakamada K, Kimura N, et al. Essential updates 2018/2019: current topics in the surgical treatment of pancreatic ductal adenocarcinoma. Ann Gastroenterol Surg. 2021;5(1):7–23. - PubMed
    1. Parikh AA, Maiga A, Bentrem D, et al. Adjuvant therapy in pancreas cancer: does it influence patterns of recurrence? J Am Coll Surg. 2016;222(4):448–56. - PubMed - PMC

LinkOut - more resources