[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332929-105":59,"doc-detail-332929-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","identify-non-mutational-p53-functional-deficiency-in-human-cancers","Identify Non-mutational p53 Functional Deficiency in Human Cancers","","An accurate assessment of p53 functional statuses is essential for cancer genomic medicine, yet non-mutational p53 inactivation cannot be detected by DNA sequencing. Such tumors are frequently misclassified as p53-normal, impairing prognosis estimation and downstream association studies. This work builds support vector machine models to reassess p53 function in TP53 wild-type tumors across multiple TCGA cohorts, achieving strong validation with AUROC 0.9822, precision 0.9747, and recall 0.9784. Results indicate 87%–99% of TP53WT tumors show compromised p53 function, with genomic instability and hypoxia, and worse overall or progression-free survival, plus increased sensitivity to platinum chemotherapy and radiotherapy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/identify-non-mutational-p53-functional-deficiency-in-human-cancers/332929/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/identify-non-mutational-p53-functional-deficiency-in-human-cancers/332929.png","ImageObject",300,407,{"name":92,"@type":93},"Theodora","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is non-mutational p53 inactivation hard to detect in cancer patients?","Question",{"text":112,"@type":113},"Because it is not identifiable through standard DNA sequencing, so tumors may be misclassified as p53-normal despite functional impairment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do the study’s SVM models reassess p53 functional status?",{"text":117,"@type":113},"The models are trained to systematically reassess p53 function in TP53 wild-type tumors using multiple TCGA cohorts and are validated through cross-validation performance metrics.",{"name":119,"@type":110,"acceptedAnswer":120},"What clinical effects are observed for TP53WT tumors with predictively reduced p53 function?",{"text":121,"@type":113},"Patients with TP53WT-pRF tumors experience significantly shorter overall survival or progression-free survival and show increased sensitivity to platinum-based chemotherapy and radiation therapy.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332929,1790217914,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},687197207919,"https://ap-avatar.wpscdn.com/avatar/a000253d6f5f7c60be?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779446848396160552","Identify Non-mutational p53 Functional Deficiency in Human Cancers  \nQianpeng Li 1,3,4,\\#, Yang Zhang 1,3,4,\\#, Sicheng Luo 1,3,4, Zhang Zhang 1,3,4, Ann L. Oberg 2, David E. Kozono 5, Hua Lu 6, Jann N. Sarkaria 7, Lina Ma 1,3,4,􀀃 , Liguo Wang 2,8,9,􀀃  \n1 National Genomics Data Center, China National Center for Bioinformation, Beijing 100101, China  \n2 Division of Computational Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA 3 Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China  \n4 University of Chinese Academy of Sciences, Beijing 100049, China  \n5 Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA 02215, USA 6 Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA  \n7 Department of Radiation Oncology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA  \n8 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA 9 Bioinformatics and Computational Biology Graduate Program, University of Minnesota Rochester, Rochester, MN 55904, USA  \n􀀃 Corresponding [authors: Wang.Liguo@mayo.edu](authors: Wang.Liguo@mayo.edu) (Wang L), [malina@big.ac.cn](malina@big.ac.cn) (Ma L) .  \n\\#Equal contribution.  \nHandling Editor: Leng Han  \nAbstract  \nAn accurate assessment of p53’s functional statuses is critical for cancer genomic medicine. However, there is a significant challenge in identifying tumors with non-mutational p53 inactivation which is not detectable through DNA sequencing. These undetected cases are often misclassified as p53-normal, leading to inaccurate prognosis and downstream association analyses. To address this issue, we built the support vector machine (SVM) models to systematically reassess p53’s functional statuses in TP53 wild-type ( TP53WT) tumors from multiple The Cancer Genome Atlas (TCGA) cohorts. Cross-validation demonstrated the good performance of the SVM models with a mean area under the receiver operating characteristic curve (AUROC) of 0.9822, precision of 0.9747, and recall of 0.9784. Our study revealed that a significant proportion (87%–99%) of TP53WT tumors actually had compromised p53 function. Additional analyses uncovered that these genetically intact but functionally impaired (termed as predictively reduced function of p53 or TP53WT-pRF) tumors exhibited genomic and pathophysiologic features akin to TP53-mutant tumors: heightened genomic instability and elevated levels of hypoxia. Clinically, patients with TP53WT-pRF tumors experienced significantly shortened overall survival or progression-free survival compared to those with predictively normal function of p53 ( TP53WT-pN) tumors, and these patients also displayed increased sensitivity to platinum-based chemotherapy and radiation therapy.  \nKey words: p53 deficiency; Cancer; DNA mutation; Composite expression; Machine learning.  \nIntroduction  \nGenetic alterations resulting in the gain or loss of gene function are major drivers of cancer development, and the identification of genomic variants through tumor DNA sequencing has significantly advanced our understanding of cancer genetics [1–3] . The most representative example is the tumor suppressor p53 (encoded by the TP53 gene), a transcription factor that plays a critical role in preventing tumorigenesis and tumor progression [4–6] . TP53 is the most frequently mutated gene that undergoes genetic inactivation in at least 20 different types of cancer [7] . Somatic mutation frequencies of TP53 exceed 50% in ovarian, esophageal, pancreatic, lung, colorectal, uterine, head and neck, oral (gingivobuccal), soft tissue (leiomyosarcoma), gastric, and biliary tract cancers [International Cancer Genome Consortium (ICGC): [https://](https://)[ ](https://)[dcc.icgc.org/genes/ENSG00000141510/mutations](dcc.icgc.org/genes/ENSG00000141510/muta","cbCaitwd0l5ucXyU","https://ap.wps.com/l/cbCaitwd0l5ucXyU","pdf",6564481,14,"English","# Abstract\n# Introduction\n## Background: p53 and TP53 mutations\n## Challenge: non-mutational p53 inactivation\n## Scope: reassessing p53 function beyond DNA sequencing\n# Methods and Evaluation\n## SVM model building on TP53WT tumors\n## Cross-validation performance metrics\n# Key Findings\n## Prevalence of predictively reduced p53 function\n## Genomic and pathophysiologic signatures\n# Clinical Implications\n## Survival outcomes\n## Response to platinum chemotherapy and radiotherapy","[{\"question\":\"Why is non-mutational p53 inactivation hard to detect in cancer patients?\",\"answer\":\"Because it is not identifiable through standard DNA sequencing, so tumors may be misclassified as p53-normal despite functional impairment.\"},{\"question\":\"How do the study’s SVM models reassess p53 functional status?\",\"answer\":\"The models are trained to systematically reassess p53 function in TP53 wild-type tumors using multiple TCGA cohorts and are validated through cross-validation performance metrics.\"},{\"question\":\"What clinical effects are observed for TP53WT tumors with predictively reduced p53 function?\",\"answer\":\"Patients with TP53WT-pRF tumors experience significantly shorter overall survival or progression-free survival and show increased sensitivity to platinum-based chemotherapy and radiation therapy.\"}]","Identify Non-mutational p53 Functional Deficiency in Human Cancers | PDF",1790000044,35]