{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:54:41Z","timestamp":1784170481958,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015992","name":"Amol University of Special Modern Technologies","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015992","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Faculty of General Medicine at Koya University, Koya, Kurdistan Region, Iraq","award":["16\/243178"],"award-info":[{"award-number":["16\/243178"]}]},{"name":"Faculty of General Medicine at Koya University, Koya, Kurdistan Region, Iraq","award":["14\/20\/29388"],"award-info":[{"award-number":["14\/20\/29388"]}]},{"DOI":"10.13039\/501100001661","name":"Institute for Anatomy and Cell Biology, University of Heidelberg, Germany","doi-asserted-by":"publisher","award":["1404.12.03"],"award-info":[{"award-number":["1404.12.03"]}],"id":[{"id":"10.13039\/501100001661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cervical cancer progression, particularly in the context of HPV infection, is driven by complex transcriptional alterations within the tumor microenvironment. Understanding the molecular mechanisms underlying HPV-induced immune evasion is crucial for developing effective therapeutic strategies. Transcriptomic analyses were performed using three independent datasets (GSE127265, GSE166466, and GSE218460) to identify differentially expressed genes (DEGs) between HPV-positive and HPV-negative cervical cancer samples. Protein\u2013protein interaction networks were constructed using Cytoscape and STRING, and immune infiltration was assessed via the TIMER database. A total of 572 DEGs were commonly identified between tumor and normal tissues, with HPV-positive samples showing distinct transcriptional profiles. Several downregulated hub genes were associated with immune regulation and receptor tyrosine kinase signaling. Immune infiltration analysis revealed altered dendritic cell and T cell patterns, indicating HPV-mediated immune modulation. Pathway enrichment identified the leukocyte transendothelial migration pathway as a key mechanism impaired by HPV infection. These findings highlight the critical role of immune-related hub genes in HPV-driven cervical cancer progression and suggest potential therapeutic targets to counteract HPV-induced immune suppression.<\/jats:p>","DOI":"10.3390\/ijms262412121","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T08:32:27Z","timestamp":1765960347000},"page":"12121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["HPV-Driven Immune Evasion in Cervical Cancer: Transcriptomic Identification of Downregulated Hub Genes and Suppressed Leukocyte Migration Pathways"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2547-5980","authenticated-orcid":false,"given":"Sana","family":"Ismael Ameen","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of General Medicine, Koya University, Koya 44023, Kurdistan Region, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0191-9042","authenticated-orcid":false,"given":"Mahla","family":"Masoudi","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Cancer, College of Biotechnology, Amol University of Special Modern Technologies, Amol 49767, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-595X","authenticated-orcid":false,"given":"Hossein","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Cancer, College of Biotechnology, Amol University of Special Modern Technologies, Amol 49767, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-1213","authenticated-orcid":false,"given":"Thomas","family":"Skutella","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Choi, S., Ismail, A., Pappas-Gogos, G., and Boussios, S. (2023). HPV and cervical cancer: A review of epidemiology and screening uptake in the UK. Pathogens, 12.","DOI":"10.3390\/pathogens12020298"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lin, T.-Y., Tsai, M.-C., Tu, W., Yeh, H.-C., Wang, S.-C., Huang, S.-P., and Li, C.-Y. (2021). Role of the NLRP3 inflammasome: Insights into cancer hallmarks. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.610492"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113625","DOI":"10.1016\/j.intimp.2024.113625","article-title":"The role of immune cells and inflammasomes in Modulating cytokine responses in HPV-Related cervical cancer","volume":"145","author":"Aghbash","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jalali, A.M., Mitchell, K.J., Pompoco, C., Poludasu, S., Tran, S., and Ramana, K.V. (2024). Therapeutic Significance of NLRP3 Inflammasome in Cancer: Friend or Foe?. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413689"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2174\/0115665232323373240905104033","article-title":"Characteristics of Oxidative Phosphorylation-Related Subtypes and Construction of a Prognostic Signature in Ovarian Cancer","volume":"25","author":"Lu","year":"2025","journal-title":"Curr. Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nagaram, S., Sen, A., Singh, V., Palani Selvam, M.R., Dwivedi, S., and Bansal, A. (Curr. Gene Ther., 2025). Role of Exosomal miRNAs and Epigenetic Modifications in Diabetic Nephropathy: Insights into Novel Diagnostic and Therapeutic Strategies, Curr. Gene Ther., in press.","DOI":"10.2174\/0115665232376803250815065514"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rangaraj, K., Vasudevan, M.T., Rangaraj, S., Kumar, R., Muthusami, S., Alahmadi, T.A., Chinnathambi, A., Arulselvan, P., Chaiyasut, C., and Bharathi, M. (Curr. Gene Ther., 2025). Synergistic Antiproliferative Effects of EGCG and Myricetin on Cervical Cancer Biomarkers in ME180 and SiHa Cell Lines, Curr. Gene Ther., in press.","DOI":"10.2174\/0115665232363374250901071820"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gakhar, M., Singh, L., Routh, S., Mukhopadhaya, A., and Singh, D.D. (Protein Pept. Lett., 2025). Evaluation of Anti-cancer Potential of Abelmoschus esculentus (Okra), Protein Pept. Lett., in press.","DOI":"10.2174\/0109298665365981250801110725"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s13046-025-03432-5","article-title":"Deciphering the tumor immune microenvironment: Single-cell and spatial transcriptomic insights into cervical cancer fibroblasts","volume":"44","author":"Lin","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Roy-Biswas, S., and Hibma, M. (2025). The Epithelial Immune Response to Human Papillomavirus Infection. Pathogens, 14.","DOI":"10.3390\/pathogens14050464"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Luo, Y., Niu, M., Liu, Y., Zhang, M., Deng, Y., Mu, D., Xu, J., and Hong, S. (2024). Oncoproteins E6 and E7 upregulate topoisomerase I to activate the cGAS-PD-L1 pathway in cervical cancer development. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1450875"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Avila, J.P., Carvalho, B.M., and Coimbra, E.C. (2023). A comprehensive view of the cancer-immunity cycle (CIC) in HPV-mediated cervical cancer and prospects for emerging therapeutic opportunities. Cancers, 15.","DOI":"10.3390\/cancers15041333"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1007\/s00262-020-02651-3","article-title":"Induction of systemic immune responses and reversion of immunosuppression in the tumor microenvironment by a therapeutic vaccine for cervical cancer","volume":"69","author":"Che","year":"2020","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e170223213775","DOI":"10.2174\/1874467216666230217151946","article-title":"Hsa_Circ_0000021 sponges miR-3940-3p\/KPNA2 expression to promote cervical cancer progression","volume":"17","author":"Zeng","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2174\/0115665232285216240228071244","article-title":"ZNF695, A Potential Prognostic Biomarker, Correlates with Im mune Infiltrates in Cervical Squamous Cell Carcinoma and Endoce rvical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification","volume":"24","author":"Ding","year":"2024","journal-title":"Curr. Gene Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shimizu, F., and Nakamori, M. (2024). Blood\u2013Brain barrier disruption in neuroimmunological disease. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202408.1175.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12974-024-03261-x","article-title":"Compromised endothelial Wnt\/\u03b2-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia","volume":"21","author":"Huang","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13045-022-01292-6","article-title":"Hypoxia-inducible factors: Master regulators of hypoxic tumor immune escape","volume":"15","author":"Wu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, J., Tang, Q., and Ren, G. (2021). Identification of UBE2C as hub gene in driving prostate cancer by integrated bioinformatics analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247827"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8810074","DOI":"10.1155\/2021\/8810074","article-title":"Identification of differentially expressed genes in cervical cancer patients by comparative transcriptome analysis","volume":"2021","author":"SD","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_21","unstructured":"Oliveros, J.C. (2025, October 03). VENNY. An Interactive Tool for Comparing Lists with Venn Diagrams. Available online: http:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21797","DOI":"10.1038\/s41598-024-72558-x","article-title":"Intelligence model on sequence-based prediction of PPI using AISSO deep concept with hyperparameter tuning process","volume":"14","author":"Thareja","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bastian, M., Heymann, S., and Jacomy, M. (2009, January 17\u201320). Gephi: An open source software for exploring and manipulating networks. Proceedings of the International AAAI Conference on Web and Social Media, San Jose, CA, USA.","DOI":"10.1609\/icwsm.v3i1.13937"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1002\/cpz1.90","article-title":"Gene set knowledge discovery with Enrichr","volume":"1","author":"Xie","year":"2021","journal-title":"Curr. 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