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This study aimed to identify EOCRC-associated genes and evaluate the functional relevance of the leading candidate. Methods: Public transcriptomic datasets were used for age-stratified candidate-gene discovery and validation. Overall survival analysis prioritized candidates, followed by loss-of-function studies and pathway-focused analyses in colorectal cancer cell lines. Results: CEMIP, NKD2, and FOXQ1 were elevated in the EOCRC groups in the discovery and integrated validation analyses. Among them, only CEMIP was significantly associated with poorer overall survival. HCT116 and HT29 cells showed relatively high endogenous CEMIP expression, and CEMIP knockdown reduced relative viable cell biomass and migration in wound-healing and Transwell assays. CEMIP-associated transcripts were enriched in several pathways, including Hedgehog, Wnt\/\u03b2-catenin, and TGF-\u03b2 signaling. In TCGA colon adenocarcinoma samples, CEMIP correlated most strongly with PTCH1; however, the correlations with other Hedgehog components were weak or absent. CEMIP silencing decreased PTCH1 and GLI1 transcripts while increasing SMO, suggesting a coordinated but non-linear relationship. Conclusions: CEMIP is an EOCRC-associated candidate biomarker and a functional contributor to colorectal cancer cell viability and migration. Its relationship with PTCH1-related Hedgehog signaling is exploratory and warrants direct mechanistic validation.<\/jats:p>","DOI":"10.3390\/genes17080922","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:08:09Z","timestamp":1785856089000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-Stratified Transcriptomic Profiling Identifies CEMIP as a Candidate Biomarker in Early-Onset Colorectal Cancer and Reveals an Association with PTCH1-Related Hedgehog Signaling"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8963-0433","authenticated-orcid":false,"given":"Chung-Ying","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital Ministry of Health and Welfare, New Taipei City 23561, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Taipei Medical University School of Medicine, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu-Jui","family":"Pan","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3580-0924","authenticated-orcid":false,"given":"Yu-Cheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hieu Duc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chun","family":"Ni","sequence":"additional","affiliation":[{"name":"PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke Xin","family":"Yee","sequence":"additional","affiliation":[{"name":"PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 235, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 23561, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Fu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Tri-Service General Hospital, National Defense Medical University, Taipei 114, Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine, National Defense Medical University, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6354-3315","authenticated-orcid":false,"given":"Kuen-Haur","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 23561, Taiwan"},{"name":"PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University-Shuangho Campus, New Taipei City 235, Taiwan"},{"name":"TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan"},{"name":"TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Transl. 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