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Cancer Lett. 2026;639:218176.

Comprehensive clinico-genomic analysis of pancreatic ductal adenocarcinoma: Overcoming biases and limitations.

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제1저자 정광록, 이종찬, 김진호 · 교신저자 황진혁

소속 (4)
  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
  2. Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; Precision Medicine Center, Future Innovation Research Division, Seoul National University Bundang Hospital, Seongnam, South Korea; Department of Genomic Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
  3. Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
  4. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. Electronic address: woltoong@snu.ac.kr.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has an exceptionally poor prognosis. Most genomic studies conducted to discover potential targets to improve PDAC prognosis have been constrained by biased cohort compositions and limited clinical information. Therefore, we aimed to develop a large-scale, unbiased, and well-organized PDAC genomic dataset. Primary pancreatic tissue samples were exclusively obtained from patients with PDAC using endoscopic ultrasound-guided fine-needle biopsy, and whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were conducted. Subsequently, comprehensive clinico-genomic analysis was performed by integrating this genomic dataset with detailed clinical information. A unique and unbiased genomic dataset, comprising 205 WES and 93 WTS datasets from 237 Asian patients with PDAC, was developed. The clinico-genomic analysis revealed distinct genetic features associated with various clinical phenotypes. Specifically, patients with liver metastasis exhibited a high frequency of TP53 mutation, increased chromosomal instability, and high frequency of copy number variants as well as KRAS allelic imbalance. Additionally, potential biomarkers derived from broad genomic data, including tumor mutation burden, mutation signatures, scar-based homologous recombination deficiency signatures, and RNA subtypes, were validated for their clinical utility. This large-scale, unbiased genomic dataset addresses the limitations of previous genomic studies in PDAC, facilitating comprehensive clinico-genomic analyses with significant clinical utility.

Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords

Asian patientClinico-genomic analysisPDACUnbiased genomic dataset

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

그 밖의 정보
출판 형태
Journal Article
저널
Cancer letters · eISSN 1872-7980
전자 출판
2025-11-26
MeSH
Humans · Carcinoma, Pancreatic Ductal* / genetics / pathology · Pancreatic Neoplasms* / genetics / pathology · Exome Sequencing · Female · Male · Mutation · Biomarkers, Tumor* / genetics · Genomics / methods · Middle Aged · Aged · DNA Copy Number Variations · Proto-Oncogene Proteins p21(ras) / genetics · Tumor Suppressor Protein p53 / genetics · Prognosis · Chromosomal Instability
Substances
Biomarkers, Tumor · Proto-Oncogene Proteins p21(ras) · KRAS protein, human · Tumor Suppressor Protein p53 · TP53 protein, human