Multi-omics analysis and functional validation of CHEK1 as an independent prognostic biomarker in Pancreatic cancer

Xiaonan Wei, Ruirong Yan, Shanshan Wang, Yaru Jiang, Haibin Li, Yanping Li

Abstract

Background

Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to challenging early diagnosis and limited treatment options. CHEK1, a crucial cell cycle regulator, is important in tumor development, but its role in pancreatic cancer remains under-researched in terms of expression, function, and regulation.

Introduction

Pancreatic cancer is characterized as a malignant neoplasm originating from the epithelial cells of the pancreatic ducts oracinar structures [1]. As reported by the International Agency for Research on Cancer (IARC), pancreatic cancer is the seventh most prevalent cancer globally and exhibits the fourth highest mortality rate among all cancers [2]. 

Materials and Methods

Analysis of CHEK1 gene expression at mRNA and protein levels

First, we analyzed the mRNA and protein expression levels of CHEK1 gene in pancreatic cancer tissues compared to normal pancreatic tissues using the UALCAN (http://ualcan.path.uab.edu/analysis.html) database. To validate these findings, we further examined CHEK1 mRNA expression using three additional independent databases including: GEPIA2 (http://gepia.cancer-pku.cn/index.html), TNMplot (https://tnmplot.com/analysis/) and the Clinical Bioinformatics Assistant (www.aclbi.com).

Results

Elevated CHEK1 levels in pancreatic cancer correlate with its pathologic grading
Initially, we conducted an investigation into the expression levels of CHEK1 using the UALCAN database. Our analysis demonstrated that CHEK1 expression was significantly elevated in pancreatic cancer compared to normal tissues, at both the mRNA and protein levels, as illustrated in Fig 1A and 1B. 

Discussion

Recent advances in tumor molecular biology have highlighted the significance of cell cycle-regulated genes in cancer development. CHEK1, a key player in cell cycle checkpoints, is essential for genomic stability [22]. Despite numerous studies on CHEK1 in various cancers, its expression and prognostic role in pancreatic cancer remain underexplored. This study aims to elucidate CHEK1’s role in pancreatic cancer using tools like multi-network and regression analyses, functional experiments, and flow cytometry analysis.

Conclusion

 In summary, high CHEK1 expression in pancreatic cancer correlates with higher pathological grades and predicts poor outcomes. Functionally, CHEK1 enhances cancer cell proliferation, migration, and cell cycle progression, which makes it a key driver of cancer progression and a potential therapeutic target (Fig 7). Further research is needed to explore CHEK1-related molecular pathways to support targeted clinical interventions for pancreatic cancer.

Acknowledgments

We appreciate all the free online databases that have helped us with our research.
Citation: Wei X, Yan R, Wang S, Jiang Y, Li H, Li Y (2026) Multi-omics analysis and functional validation of CHEK1 as an independent prognostic biomarker in Pancreatic cancer. PLoS One 21(1): e0340878. https://doi.org/10.1371/journal.pone.0340878

Editor: Hamidreza Montazeri Aliabadi, Chapman University, UNITED STATES OF AMERICA

Received: August 29, 2025; Accepted: December 29, 2025; Published: January 21, 2026

Copyright: © 2026 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This research was supported by the National Natural Science Foundation of China ( No. 82002961, Yanping Li; No. 82101867, Shanshan Wang ). The funding agencies had no involvement in the research design, data acquisition, data analysis and interpretation, nor in the writing of the manuscript.

Competing interests: The authors declare no conflicts of interest related to this study.

Abbreviations: CHEK1, Checkpoint kinase 1; OS, Overall Survival; G2/M, Gap 2 phase/Mitosis phase; ROC, Receiver Operating Characteristic; AUC, Area Under roc Curve