Transcriptomics and Mendelian randomization studies reveal the critical role of Stanniocalcin-2 in linking perfluorinated compound-exposure to colorectal cancer

Sep 22, 2026

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Colorectal carcinoma (CRC) is a leading gastrointestinal malignancy with persistently high morbidity, mortality, and recurrence, driving the need for more precise prognostic biomarkers. Using transcriptomic data from 638 CRC and 51 normal controls, researchers identified 3,230 PFC-associated genes and prioritized prognostic candidates through differential expression, enrichment, and PPI analyses. A LASSO model (PRAME, CDKN2A, STC2) was validated with Kaplan–Meier and ROC analyses, and MR plus experiments supported STC2 as a mediator linking PFC exposure to CRC risk, including PFOA-driven STC2 upregulation.

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CategoryResearch & Report

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Introduction

TYPE Original Research PUBLISHED 28 April 2026 DOI 10.3389/fpubh.2026.1768633 OPEN ACCESS EDITED BY Ricardo Assunção, National Health Institute Doutor Ricardo Jorge (INSA), Portugal REVIEWED BY Shang Zhihao, Beijing University of Chinese Medicine, China Kai Liu, National Center For Occupational Safety And Health, China *CORRESPONDENCE Rui Zhang [zhangrui1981@hebmu.edu.cn](zhangrui1981@hebmu.edu.cn)[ ](zhangrui1981@hebmu.edu.cn)Shunjiang Xu [xushunjiang@hebmu.edu.cn](xushunjiang@hebmu.edu.cn) †These authors have contributed equally to this work RECEIVED 16 December 2025 REVISED 27 March 2026 ACCEPTED 07 April 2026 PUBLISHED 28 April 2026 CITATION Li B, Yang Q, Wu J, Zheng J, Zhao N, Gao Z, Luo Y, Zhang R and Xu S (2026) Transcriptomics and Mendelian randomization studies reveal the critical role of Stanniocalcin-2 in linking perfluorinated compound-exposure to colorectal cancer. Front. Public Health 14:1768633 . doi: 10.3389/fpubh.2026.1768633 COPYRIGHT © 2026 Li, Yang, Wu, Zheng, Zhao, Gao, Luo, Zhang and Xu. 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. Transcriptomics and Mendelian randomization studies reveal the critical role of Stanniocalcin-2 in linking perfluorinated compound-exposure to colorectal cancer Bingxin Li 1 , 2†, Qianqian Yang3†, Jianghui Wu 2,4, Jiahui Zheng 5, Na Zhao 1 ,6, Zhaoyu Gao 1 ,6, Yang Luo 1 ,6, Rui Zhang1 ,6* and Shunjiang Xu1 ,6* 1Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China, 2Department of Pathophysiology, Hebei Medical University, Shijiazhuang, China, 3Clinical Pharmacy Department, The First Hospital of Hebei Medical University, Shijiazhuang, China, 4Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, China, 5Department of Information and Computing Science, Jinan University – University of Birmingham Joint Institute at Jinan University, Guangzhou, China, 6Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, China Colorectal carcinoma (CRC) represents a major gastrointestinal malignancy with substantial global incidence, marked by elevated morbidity and mortality rates. Despite advancements in treatment, there is still considerable variation in prognosis, particularly with high recurrence rates, emphasizing the need for more precise prognostic tools. The present study is aimed at identifying central prognostic biomarkers linked to perfluorinated compound (PFCs) exposure and construct a prognostic risk model for CRC based on transcriptomic data. We analyzed transcriptome data from 638 CRC samples and 51 normal control samples from The Cancer Genome Atlas (TCGA) database, then identified a total of 3,230 PFC-associated genes. Candidate genes related to CRC prognosis were found by analyzing differences in gene expression, doing functional enrichment, and building a protein–protein interaction (PPI) network. We built a LASSO model with PRAME, CDKN2A, and STC2 and checked it using Kaplan–Meier analysis and ROC curves over time, while STC2 was further identified as the key mediator linking PFC exposure to CRC risk based on Mendelian randomization and experimental validation. This model could put patients into high-risk or low-risk groups, which gives doctors a new tool to plan personalized treatments. We also checked the immune setting, tumor mutation load, and likely response to immunotherapy, which further proved the model’s usefulness in the clinic. A Mendelian randomization (MR) analysis in two steps showed that higher levels of ge

FAQs

What was the study designed to identify for colorectal cancer patients?

To identify central prognostic biomarkers related to perfluorinated compound (PFC) exposure and to construct a CRC prognostic risk model based on transcriptomic data.

How were prognosis-related genes selected from transcriptomic data?

The study analyzed transcriptome differences between CRC and normal controls, performed functional enrichment, and built a protein–protein interaction (PPI) network to find candidate genes tied to CRC prognosis.

What evidence supports Stanniocalcin-2 (STC2) as a mediator between PFC exposure and CRC risk?

Two-step Mendelian randomization showed increased CRC risk with genetic risk for PFOA and PFOS exposure, and STC2 partially explained the mediating effect; in vitro experiments further showed PFOA upregulates STC2 transcription in CRC cells.

Sep 22, 2026

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