{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:36:00Z","timestamp":1777358160821,"version":"3.51.4"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>\n                    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\u2013protein interaction (PPI) network. We built a LASSO model with PRAME, CDKN2A, and STC2 and checked it using Kaplan\u2013Meier 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\u2019s usefulness in the clinic. A Mendelian randomization (MR) analysis in two steps showed that higher levels of genetic risk for Perfluorooctanoic acid (PFOA) and Perfluorooctanesulfonic acid (PFOS) exposure raised CRC risk. STC2 was found to partly explain the mediator from PFOA to CRC, making up about 8.6% of the overall effect. We ran sensitivity checks, and the results still held, which means these cause-and-effect findings are strong. Finally,\n                    <jats:italic>In vitro<\/jats:italic>\n                    analyses verified that PFOA upregulates STC2 transcription in CRC cells. Our results suggest new ways to assess CRC prognosis and give scientific backing for treating cancers linked to the environment, based on how PFCs work in the body.\n                  <\/jats:p>","DOI":"10.3389\/fpubh.2026.1768633","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:39:04Z","timestamp":1777354744000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomics and Mendelian randomization studies reveal the critical role of Stanniocalcin-2 in linking perfluorinated compound-exposure to colorectal cancer"],"prefix":"10.3389","volume":"14","author":[{"given":"Bingxin","family":"Li","sequence":"first","affiliation":[{"name":"Central Laboratory, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Department of Pathophysiology, Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianghui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Critical Disease Mechanism and Intervention","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Information and Computing Science, Jinan University \u2013 University of Birmingham Joint Institute at Jinan University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Zhao","sequence":"additional","affiliation":[{"name":"Central Laboratory, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Central Laboratory, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Luo","sequence":"additional","affiliation":[{"name":"Central Laboratory, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Central Laboratory, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunjiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Central Laboratory, The First Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease","place":["Shijiazhuang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1136\/gutjnl-2022-328845","article-title":"Targeting m6A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer","volume":"72","author":"Bao","year":"2023","journal-title":"Gut"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s13046-020-01690-z","article-title":"TM4SF1 promotes EMT and cancer stemness via the Wnt\/\u03b2-catenin\/SOX2 pathway in colorectal cancer","volume":"39","author":"Tang","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s12967-024-04955-9","article-title":"A multi-dimensional approach to unravel the intricacies of lactylation related signature for prognostic and therapeutic insight in colorectal 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