Characterisation of early-onset pancreatic adenocarcinoma molecular profile compared to average-onset pancreatic adenocarcinoma (CARAPAC): A systematic review and a meta-analysis

IF 2.7 2区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Pancreatology Pub Date : 2026-05-01 Epub Date: 2026-03-03 DOI:10.1016/j.pan.2026.03.002

Mathias Brugel , Vivien Riviere , Audrey Hubert , Léonie Langanay , Olivier Bouche , Michaël Genin , Victoria Gauthier , Jean-Baptiste Oudart

{"title":"Characterisation of early-onset pancreatic adenocarcinoma molecular profile compared to average-onset pancreatic adenocarcinoma (CARAPAC): A systematic review and a meta-analysis","authors":"Mathias Brugel , Vivien Riviere , Audrey Hubert , Léonie Langanay , Olivier Bouche , Michaël Genin , Victoria Gauthier , Jean-Baptiste Oudart","doi":"10.1016/j.pan.2026.03.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Early-onset pancreatic adenocarcinoma (EOPA), defined as the diagnosis of pancreatic adenocarcinoma before the age of 50, is increasingly reported and may differ molecularly from average-onset pancreatic adenocarcinoma (AOPA). Understanding these differences is essential for precision medicine in this poor-prognosis malignancy.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies published between 2015 and 2025 reporting molecular data on EOPA and/or AOPA were identified. Comparative studies stratified by age group for molecular alterations were included in the meta-analysis. Quality assessment was performed using the JBI checklist. This study aimed at systematically review and meta-analyse existing data comparing the molecular landscape of EOPA and AOPA, and evaluate whether EOPA constitutes a distinct molecular subgroup of pancreatic adenocarcinoma.</div></div><div><h3>Results</h3><div>Thirty-nine articles were included in the systematic review, of which eight met criteria for meta-analysis. <em>KRAS</em> mutations were significantly less frequent in EOPA than in AOPA (OR = 0.61; 95%CI [0.43–0.86], p = 0.005). No significant differences were observed for <em>TP53, CDKN2A, SMAD4</em>, or <em>BRCA1/2</em> alterations. Sensitivity analyses confirmed the robustness of the <em>KRAS</em> finding. Study heterogeneity was moderate (I<sup>2</sup> = 40%). Quality assessment revealed substantial variability in design, molecular methods, and reporting standards.</div></div><div><h3>Conclusions</h3><div>EOPA is enriched in <em>KRAS</em> wild-type tumours. This profile may offer alternative therapeutic opportunities, including RNA-based fusion detection, inclusion in targeted therapy trials, and suggest alternative oncogenic pathways for a proportion of this subpopulation. Standardised definitions, consistent molecular reporting, and exploration of age-specific risk factors are critical to improve understanding and management of EOPA.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"26 3","pages":"Pages 421-427"},"PeriodicalIF":2.7000,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pancreatology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1424390326001225","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/3/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Early-onset pancreatic adenocarcinoma (EOPA), defined as the diagnosis of pancreatic adenocarcinoma before the age of 50, is increasingly reported and may differ molecularly from average-onset pancreatic adenocarcinoma (AOPA). Understanding these differences is essential for precision medicine in this poor-prognosis malignancy.

Methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies published between 2015 and 2025 reporting molecular data on EOPA and/or AOPA were identified. Comparative studies stratified by age group for molecular alterations were included in the meta-analysis. Quality assessment was performed using the JBI checklist. This study aimed at systematically review and meta-analyse existing data comparing the molecular landscape of EOPA and AOPA, and evaluate whether EOPA constitutes a distinct molecular subgroup of pancreatic adenocarcinoma.

Results

Thirty-nine articles were included in the systematic review, of which eight met criteria for meta-analysis. KRAS mutations were significantly less frequent in EOPA than in AOPA (OR = 0.61; 95%CI [0.43–0.86], p = 0.005). No significant differences were observed for TP53, CDKN2A, SMAD4, or BRCA1/2 alterations. Sensitivity analyses confirmed the robustness of the KRAS finding. Study heterogeneity was moderate (I² = 40%). Quality assessment revealed substantial variability in design, molecular methods, and reporting standards.

Conclusions

EOPA is enriched in KRAS wild-type tumours. This profile may offer alternative therapeutic opportunities, including RNA-based fusion detection, inclusion in targeted therapy trials, and suggest alternative oncogenic pathways for a proportion of this subpopulation. Standardised definitions, consistent molecular reporting, and exploration of age-specific risk factors are critical to improve understanding and management of EOPA.

查看原文本刊更多论文

早发性胰腺腺癌分子特征与平均发性胰腺腺癌（CARAPAC）的比较：一项系统综述和荟萃分析。

背景：早发性胰腺腺癌（EOPA），定义为50岁前诊断的胰腺腺癌，越来越多的报道，可能与平均起病胰腺腺癌（AOPA）在分子上有所不同。了解这些差异对于精准治疗这种预后不良的恶性肿瘤至关重要。方法：根据PRISMA指南进行系统评价和荟萃分析。2015年至2025年间发表的报告EOPA和/或AOPA分子数据的研究被确定。meta分析包括按年龄组分层的分子改变的比较研究。使用JBI检查表进行质量评估。本研究旨在系统回顾和荟萃分析现有数据，比较EOPA和AOPA的分子格局，并评估EOPA是否构成胰腺腺癌的不同分子亚群。结果：系统评价纳入39篇文章，其中8篇符合meta分析标准。KRAS突变在EOPA中的发生率明显低于AOPA （OR = 0.61; 95%CI [0.43-0.86], p = 0.005）。TP53、CDKN2A、SMAD4或BRCA1/2的改变没有显著差异。敏感性分析证实了KRAS结果的稳健性。研究异质性为中等（I2 = 40%）。质量评估揭示了在设计、分子方法和报告标准方面的实质性变化。结论：EOPA在KRAS野生型肿瘤中富集。这一特征可能提供替代治疗机会，包括基于rna的融合检测，纳入靶向治疗试验，并为这一亚群的一部分提供替代的致癌途径。标准化的定义、一致的分子报告和对年龄特异性危险因素的探索对于提高对EOPA的理解和管理至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pancreatology 医学-胃肠肝病学

CiteScore

7.20

自引率

5.60%

发文量

194

审稿时长

44 days

期刊介绍： Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.