Determination and characterization of molecular heterogeneity and precision medicine strategies of patients with pancreatic cancer and pancreatic neuroendocrine tumor based on oxidative stress and mitochondrial dysfunction-related genes

Sep 24, 2026

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Mitochondria regulate both cellular energy production and reactive oxygen/nitrogen species generation, yet the integrated roles of oxidative stress–related mitochondrial genes (MTGs-OS) in pancreatic cancer and pancreatic neuroendocrine tumors remain insufficiently defined. Comprehensive pan-cancer analyses evaluated expression patterns, prognostic impact, mutation, methylation, and pathway interactions. Patients were stratified into MTGs-OS–based clusters, and a LASSO-derived prognostic model for pancreatic cancer was validated using qRT-PCR, yielding subtype-specific survival and tumor-immune microenvironment differences.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Background

Methods

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Introduction

TYPE Original Research PUBLISHED 08 May 2023 DOI 10.3389/fendo.2023.1127441 OPEN ACCESS EDITED BY Ralf Jockers, Universite´ Paris Cite´, France REVIEWED BY Bela Ozsvari, University of Salford, United Kingdom Milica B. Markelic, University of Belgrade, Serbia *CORRESPONDENCE Changmiao Wang [wangchangmiaodl@sina.cn](wangchangmiaodl@sina.cn)[ ](wangchangmiaodl@sina.cn)Wenzhi Liu [liuwenzhi1965@163.com](liuwenzhi1965@163.com)[ ](liuwenzhi1965@163.com)Ning Li [lining_19850101@hotmail.com](lining_19850101@hotmail.com) †These authors have contributed equally to this work RECEIVED 19 December 2022 ACCEPTED 15 March 2023 PUBLISHED 08 May 2023 CITATION Cui Y, Yuan Q, Chen J, Jiang J, Guan H, Zhu R, Li N, Liu W and Wang C (2023) Determination and characterization of molecular heterogeneity and precision medicine strategies of patients with pancreatic cancer and pancreatic neuroendocrine tumor based on oxidative stress and mitochondrial dysfunction-related genes. Front. Endocrinol. 14:1127441 . doi: 10.3389/fendo.2023.1127441 COPYRIGHT © 2023 Cui, Yuan, Chen, Jiang, Guan, Zhu, Li, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Determination and characterization of molecular heterogeneity and precision medicine strategies of patients with pancreatic cancer and pancreatic neuroendocrine tumor based on oxidative stress and mitochondrial dysfunction-related genes Yougang Cui 1,2†, Qihang Yuan 1†, Junhong Chen 3†, Jian Jiang 1†, Hewen Guan 4, Ruiping Zhu 5, Ning Li 1,6*, Wenzhi Liu 2* and Changmiao Wang 1* 1 Department of General Surgery, The First Afﬁliated Hospital of Dalian Medical University, Dalian, Liaoning, China, 2 Department of Gastrointestinal Surgery, The Afﬁliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China, 3 Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, China, 4 Department of Dermatology, The First Afﬁliated Hospital of Dalian Medical University, Dalian, Liaoning, China, 5 Department of Pathology, Afﬁliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China, 6 Department of General Surgery, Wafangdian Central Hospital, Dalian, Liaoning, China Background: Mitochondria are signiﬁcant both for cellular energy production and reactive oxygen/nitrogen species formation. However, the signiﬁcant functions of mitochondrial genes related to oxidative stress (MTGs-OS) in pancreatic cancer (PC) and pancreatic neuroendocrine tumor (PNET) are yet to be investigated integrally. Therefore, in pan-cancer, particularly PC and PNET, a thorough assessment of the MTGs-OS is required. Methods: Expression patterns, prognostic signiﬁcance, mutation data, methylation rates, and pathway-regulation interactions were studied to comprehensively elucidate the involvement of MTGs-OS in pan-cancer. Next, we separated the 930 PC and 226 PNET patients into 3 clusters according to MTGs-OS expression and MTGs-OS scores. LASSO regression analysis was utilized to construct a novel prognostic model for PC. qRT-PCR(Quantitative real-time PCR) experiments were performed to verify the expression levels of model genes. Results: The subtype associated with the poorest prognosis and lowerest MTGsOS scores was Cluster 3, which could demonstrate the vital function of MTGs-OS for the pathophysiological processes of PC. The three clusters displayed distinct variations in the expression of conventional cancer-associated genes and the Frontiers in Endocrinology 01 [frontiersin.org](frontier

FAQs

What role do oxidative stress–related mitochondrial genes (MTGs-OS) play in pancreatic cancer and pancreatic neuroendocrine tumors?

The study focuses on MTGs-OS as drivers linked to disease progression and prognostic differences in both pancreatic cancer and pancreatic neuroendocrine tumors, by assessing their expression and biological associations.

How were patients grouped in the analysis?

The study separated 930 pancreatic cancer and 226 PNET patients into three clusters based on MTGs-OS expression patterns and MTGs-OS scores.

How was the prognostic model for pancreatic cancer constructed and validated?

A novel prognostic model was built using LASSO regression, then qRT-PCR experiments verified expression levels of model genes and datasets (training, internal validation, external validation) were used to categorize patients into high- vs low-risk groups.

Sep 24, 2026

Uploaded by Miles