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This study examines expression changes of CDKN2A, ITGA3, SMAD4, and SIRT7 in human cSCC tumor tissue compared with matched normal skin, and evaluates their diagnostic biomarker potential. qPCR profiling of AJCC-8 T2 samples (n=26) combined with ROC analysis identifies discriminatory expression patterns, supported by interaction and comparative expression analyses. Findings support these genes as candidate diagnostic molecular biomarkers.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/cdkn2a-itga3-smad4-and-sirt7-gene-expression-in-human-cutaneous-squamous-cell-carcinoma-development-and-pre-clinical-diagnosis/349189/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/cdkn2a-itga3-smad4-and-sirt7-gene-expression-in-human-cutaneous-squamous-cell-carcinoma-development-and-pre-clinical-diagnosis/349189.png","ImageObject",300,407,{"name":42,"@type":43},"Cipher","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":22},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Which genes were assessed for expression changes in human cSCC, and how were they compared?","Question",{"text":62,"@type":63},"CDKN2A, ITGA3, SMAD4, and SIRT7 were measured in cSCC tumor tissue and compared with matched normal skin using qPCR.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What did the study find about gene expression differences between tumors and matched normal skin?",{"text":67,"@type":63},"ITGA3 and SIRT7 expression increased, while CDKN2A and SMAD4 expression decreased in cSCC versus matched normal skin.",{"name":69,"@type":60,"acceptedAnswer":70},"How was diagnostic potential evaluated for these gene expression markers?",{"text":71,"@type":63},"Diagnostic power was assessed using ROC analysis to test how efficiently target gene expression discriminates cSCC from normal skin.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},349189,1790226251,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":22,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},687208528416,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Khidhir etal. BMC Cancer (2026) 26:622 BMC Cancer  \n[https://doi.org/10.1186/s12885-026-15918-2](https://doi.org/10.1186/s12885-026-15918-2)  \nRESEARCH Open Access  \nCDKN2A, ITGA3, SMAD4 and SIRT7 gene  expression in human cutaneous squamous  \ncell carcinoma development and pre-clinical diagnosis  \nKarzan G. Khidhir 1*, Dana K. Sabir2, Abbas Salihi3,4 and Benjamin H. Miranda5,6*  \nAbstract  \nBackground Cutaneous squamous cell carcinoma (cSCC) is the second most frequent cause of skin cancer death after melanoma. An improved understanding of molecular mechanisms will likely contribute to the development of improved diagnostic and treatment strategies. We investigated changes in the expression of CDKN2A, ITGA3, SMAD4, and SIRT7 in human cSCC tumor tissue versus matched normal skin, and assessed their potential for use as diagnostic biomarkers.  \nMethods Stage T2 (AJCC-8) cSCC tumor and normal tissue were collected (n = 26), qPCR was performed to detect relative target gene expression, and ROC analysis was undertaken to investigate diagnostic power of these genes. The GENT2 and DepMap were used to compare target gene expression profiles in different human cancer tissues and cell lines, and a gene-gene interaction network was generated using GeneMANIA.  \nResults The qPCR indicated an increase in ITGA3 (2 . 2-fold) and SIRT7 (1 . 5 fold), and a decrease in CDKN2A (-1 .1 fold) and SMAD4 (-0 . 75) expression, in cSCC versus matched normal skin. The gene-gene interaction network showed co-expression of CDKN2A and SMAD4 and physical interactions between ITGA3 and SIRT7. ROC analysis indicated that target gene expression could efficiently discriminate cSCC from normal skin, supporting their potential use as diagnostic molecular biomarkers.  \nConclusions CDKN2A, ITGA3, SMAD4 and SIRT7 genes are involved in human cSCC development and have the potential for use as diagnostic molecular biomarkers; these findings should contribute to the development of novel diagnostic and therapeutic strategies.  \nKeywords Molecular Biomarker, CDKN2A, cSCC, ITGA3, SMAD4, SIRT7  \n*Correspondence:  \nKarzan G. Khidhir[karzan.khidhir@univsul.edu.iq](karzan.khidhir@univsul.edu.iq)[ ](karzan.khidhir@univsul.edu.iq)Benjamin H. Miranda  \n[Ben.Miranda@nhs.net](Ben.Miranda@nhs.net); [Ben.Miranda@aru.ac.uk](Ben.Miranda@aru.ac.uk)  \n1Department of Biology, College of Science, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq  \n2Department of Medical Laboratory Sciences, Charmo University, Chamchamal, Kurdistan Region, Iraq  \n3Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq  \n4Center of Research and Strategic Studies, Lebanese French University, Erbil, Kurdistan Region 44002, Iraq  \n5St Andrew’s Centre for Plastic Surgery & Burns, Broomfield Hospital, Chelmsford, UK  \n6St Andrew’s Anglia Ruskin (StAAR) Research Group, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Chelmsford, UK  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://crea","cbCaioywHuyUBrJm","https://ap.wps.com/l/cbCaioywHuyUBrJm","pdf",4827380,13,"English","# Abstract\n# Introduction\n## Molecular mechanisms and risk factors in cSCC\n## Diagnosis and treatment approaches","[{\"question\":\"Which genes were assessed for expression changes in human cSCC, and how were they compared?\",\"answer\":\"CDKN2A, ITGA3, SMAD4, and SIRT7 were measured in cSCC tumor tissue and compared with matched normal skin using qPCR.\"},{\"question\":\"What did the study find about gene expression differences between tumors and matched normal skin?\",\"answer\":\"ITGA3 and SIRT7 expression increased, while CDKN2A and SMAD4 expression decreased in cSCC versus matched normal skin.\"},{\"question\":\"How was diagnostic potential evaluated for these gene expression markers?\",\"answer\":\"Diagnostic power was assessed using ROC analysis to test how efficiently target gene expression discriminates cSCC from normal skin.\"}]","CDKN2A, ITGA3, SMAD4 and SIRT7 gene expression in human cutaneous squamous cell carcinoma development and pre-clinical diagnosis | PDF",1790082113,33]