{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:06:59Z","timestamp":1778213219609,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Scientific Research Foundation of Guangdong Province, China","award":["B2023050"],"award-info":[{"award-number":["B2023050"]}]},{"name":"Natural Science Foundation of Guangdong Province, China","award":["2023A1515010530"],"award-info":[{"award-number":["2023A1515010530"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for reliable biomarkers and therapeutic targets. To address this need, we focused on UDP-glucose pyrophosphorylase 2 (UGP2). Although UGP2 has been implicated in tumorigenesis across multiple cancers, its precise role and clinical significance in CRC remain poorly understood. This study aimed to comprehensively characterize UGP2 in CRC through an integrated approach encompassing proteomic screening, bioinformatics analysis, and experimental validation. We identified UGP2 as a significantly downregulated tumor-suppressive factor in CRC. Specifically, UGP2 expression was significantly downregulated in CRC tissues compared with that in normal controls and exhibited strong correlations with aggressive clinicopathological features, including lymphatic invasion, perineural invasion, and colon polyp history, and patient age. It also demonstrated high diagnostic accuracy in CRC, with an area under the receiver operating characteristic curve (AUC) of 0.990. Reduced UGP2 levels were associated with poorer overall survival and disease-specific survival. Hypermethylation of the UGP2 promoter correlated with a favorable prognosis in patients with CRC. UGP2 expression positively correlated with immune cell infiltration within the tumor microenvironment. Functionally, UGP2 knockdown increased CRC cell proliferation and migration while suppressing apoptosis. Conversely, its overexpression yielded the opposite effects, confirming UGP2\u2019s role in constraining malignant phenotypes. Collectively, these findings establish UGP2 as a key CRC tumor suppressor whose downregulation drives malignant progression and predicts adverse clinical outcomes, suggesting its potential as a dual-purpose diagnostic and prognostic biomarker.<\/jats:p>","DOI":"10.3390\/cimb47121043","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"1043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of UGP2 as a Biomarker in Colorectal Cancer: Implications for Tumor Progression, Diagnosis, and Prognosis"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3059-8451","authenticated-orcid":false,"given":"Lijiao","family":"Cui","sequence":"first","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China"},{"name":"Laboratory of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-5586","authenticated-orcid":false,"given":"Caiyuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7663-7379","authenticated-orcid":false,"given":"Shicai","family":"Ye","sequence":"additional","affiliation":[{"name":"Laboratory of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China"},{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9960-9134","authenticated-orcid":false,"given":"Yuee","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Second People\u2019s Hospital of Nanhai District, Foshan 528000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0980-4667","authenticated-orcid":false,"given":"Zhiwei","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2951-8108","authenticated-orcid":false,"given":"Vincent Kam Wai","family":"Wong","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China"},{"name":"Innovation Technology Research Institute, Macau University of Science and Technology, Macao SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6183-6261","authenticated-orcid":false,"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China"},{"name":"Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"ref_1","first-page":"1989","article-title":"Associations of circulating leptin levels with colorectal adenoma and colorectal cancer: A case-control and Mendelian randomization study","volume":"43","author":"Zhao","year":"2023","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tsang, H.F., Pei, X.M., Wong, Y.K.E., and Wong, S.C.C. 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