{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:04:54Z","timestamp":1780031094392,"version":"3.53.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003454","name":"Guangxi Zhuang Autonomous Region Health Department","doi-asserted-by":"publisher","award":["Z-K20231763"],"award-info":[{"award-number":["Z-K20231763"]}],"id":[{"id":"10.13039\/501100003454","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"\n Background<\/jats:title>\n \n Origin Recognition Complex Subunit 6 (\n ORC6<\/jats:italic>\n ) is essential for DNA replication initiation. However, its dynamic expression patterns and potential biological functions during the progression of cervical lesions remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We analyzed the differential expression of\n ORC6<\/jats:italic>\n in cervical cancer and normal tissues using an integrated TCGA-GTEx-CESC dataset and explored its potential regulatory mechanisms via GO\/KEGG, GSEA, and CIBERSORT immune infiltration analyses. Furthermore, a total of 163 clinical tissue specimens (including CIN I, CIN II, CIN III, and invasive cervical carcinoma) were examined by immunohistochemistry (IHC) to evaluate\n ORC6<\/jats:italic>\n protein expression and its association with pathological grade and clinicopathological characteristics.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Bioinformatics analysis revealed that\n ORC6<\/jats:italic>\n was significantly upregulated in cervical cancer (\n P<\/jats:italic>\n \u00a0&lt;\u00a00.001) and was associated with transcriptional programs related to E2F targets, DNA replication, and the G2\/M checkpoint. Immune infiltration analysis showed that elevated\n ORC6<\/jats:italic>\n expression was associated with a distinct immune infiltration pattern, characterized by increased M0 macrophages and reduced activated NK cells, resting NK cells, and CD8+ T cells. IHC analysis further demonstrated that\n ORC6<\/jats:italic>\n expression was significantly increased in cervical lesions and invasive carcinoma compared with normal cervical tissues (\n P<\/jats:italic>\n &lt;\u00a00.001). Notably,\n ORC6<\/jats:italic>\n expression was significantly higher in the CIN II\u2013III group than in the CIN I group (\n P<\/jats:italic>\n &lt;\u00a00.01). In contrast,\n ORC6<\/jats:italic>\n expression was not significantly associated with tumor differentiation, lymph node metastasis, vascular invasion, perineural invasion, or overall survival (all\n P<\/jats:italic>\n &gt; 0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n ORC6<\/jats:italic>\n is closely associated with the progression of HPV-related cervical lesions, particularly the transition from CIN I to CIN II\u2013III.\n ORC6<\/jats:italic>\n may serve as a potential auxiliary biomarker for the identification and early stratification of high-grade squamous intraepithelial lesions (HSIL).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fonc.2026.1795793","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:47:03Z","timestamp":1780030023000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ORC6 drives the malignant progression of cervical squamous intraepithelial lesions and serves as a biomarker for high-grade dysplasia"],"prefix":"10.3389","volume":"16","author":[{"given":"Rouyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feihu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyan","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First People\u2019s Hospital of Yulin","place":["Yulin, 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