{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:04:36Z","timestamp":1792605876367,"version":"4.5.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"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. Immunol."],"abstract":"<jats:p>Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (<jats:italic>PLOD3<\/jats:italic>) is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. <jats:italic>PLOD3<\/jats:italic> expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of <jats:italic>PLOD3<\/jats:italic>-related genes. The correlation between <jats:italic>PLOD3<\/jats:italic> expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of <jats:italic>PLOD3<\/jats:italic> in CRC. What\u2019s more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. <jats:italic>PLOD3<\/jats:italic> was highly expressed in many tumors including CRC. <jats:italic>PLOD3<\/jats:italic> was upregulated in advanced stage CRCs, and high <jats:italic>PLOD3<\/jats:italic> expression was associated with poor survival. High <jats:italic>PLOD3<\/jats:italic> expression was associated with low levels of B cells, CD4<jats:sup>+<\/jats:sup> T cells, M1 macrophages, CD8<jats:sup>+<\/jats:sup> T cells, and multiple immunerelated characteristics. In addition, the high <jats:italic>PLOD3<\/jats:italic> expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high <jats:italic>PLOD3<\/jats:italic> expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of <jats:italic>PLOD3<\/jats:italic> at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased <jats:italic>PLOD3<\/jats:italic> expression in an immunotherapy treated dataset. <jats:italic>PLOD3<\/jats:italic> is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high <jats:italic>PLOD3<\/jats:italic> expression may be resistant to immune checkpoint therapy.<\/jats:p>","DOI":"10.3389\/fimmu.2021.722807","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T16:38:20Z","timestamp":1632760700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Integrated Profiling Identifies PLOD3 as a Potential Prognostic and Immunotherapy Relevant Biomarker in Colorectal 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