Evidence map›Paper›PMID 42398462›Full record

ArticleTranslational oncology2026

REG4 serves as a prognostic biomarker for pancreatic cancer with long-standing diabetes mellitus by modulating chemoresistance.

Jae-Il Choi, Hee Jung Park, Hak Park, Yonggeun Cho, Hyo Shik Shin, Young Ik Koh, See Young Lee, Sung Ill Jang, Jae Hee Cho, Hyung Sun Kim and 3 more

Abstract read
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Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Jae-Il ChoiDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Pathology, Ajou University School of Medicine, Suwon, Republic of Korea.
Hee Jung ParkDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Hak ParkDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China.
Yonggeun ChoDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Hyo Shik ShinDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Young Ik KohDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
See Young LeeInstitute of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sung Ill JangInstitute of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jae Hee ChoInstitute of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Hyung Sun KimDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Ho Kyoung HwangDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
John Hoon RimDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: johnhoon1@yuhs.ac.
Jong-Baeck LimDepartment of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: jlim@yuhs.ac.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPancreatic ductal adenocarcinoma (PDAC) in patients with diabetes mellitus (DM) represents a clinically heterogeneous subgroup, yet biomarkers that reflect diabetes-associated tumor biology and chemotherapy response remain limited. In particular, the influence of diabetes duration on treatment resistance in PDAC is poorly understood.

methodsWe performed an integrated translational analysis combining reanalysis of public single-cell RNA sequencing (scRNA-seq) datasets, clinical serum biomarker profiling, and functional validation using pancreatic cancer cell lines and patient-derived organoids. Circulating REG4 concentrations were measured in independent PDAC cohorts and correlated with diabetes duration, overall survival, and response to FOLFIRINOX. Functional relevance was assessed under diabetes-mimicking hyperglycemic conditions.

resultsSingle-cell transcriptomic analysis demonstrated enrichment of REG4-expressing tumor cells within the classical PDAC subtype specifically in diabetic patients. Clinically, circulating REG4 concentrations were significantly elevated in PDAC patients with long-standing diabetes, and high REG4 levels were associated with poor overall survival and resistance to FOLFIRINOX exclusively in this subgroup. In contrast, no prognostic association was observed in non-diabetic or new-onset diabetic patients. In patient-derived organoids and pancreatic cancer cell lines, chronic glucose exposure induced REG4 expression, activation of WNT/β-catenin signaling, suppression of apoptotic pathways, and increased resistance to FOLFIRINOX, recapitulating key clinical features of long-standing diabetes-associated PDAC.

conclusionsThese findings suggest REG4 as a candidate diabetes duration-dependent prognostic and predictive biomarker in pancreatic cancer, warranting validation in larger prospective cohorts. By linking metabolic context to chemotherapy resistance through REG4-associated signaling, this study provides a translational framework for patient stratification and treatment optimization in diabetes-associated PDAC.

Indexed as

ChemoresistanceDiabetes mellitusFOLFIRINOXPancreatic cancerREG4

Identifiers

PMID42398462
PMCPMC13355485

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.