[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-117546-en":3,"doc-seo-117546-105":30,"detail-sidebar-cat-0-en-105":88},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":20,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},117546,687197207057,"Sage","https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0",8,"Research & Report","Machine Learning-Derived Neddylation Gene Signature for Predicting Prognosis and Immunotherapy Benefits in Colorectal Cancer","Colorectal cancer remains a leading cause of cancer mortality largely because treatment resistance limits effective therapy. This study investigates neddylation-related genes and their impact on tumor biology and immune responses in CRC. Using CRC single-cell RNA-seq from TISCH, TCGA and GEO bulk RNA-seq clustering, and ten machine-learning algorithms, the work builds and externally validates a neddylation-related gene signature (NRGS). NRGS-high cases show worse survival, more immunosuppressive microenvironment features, higher recurrence/metastasis associations, advanced stage links, and potential resistance to immunotherapy and standard chemotherapy.","ImmunoTargets and Therapy downloaded from [https://www.dovepress.com/](https://www.dovepress.com/)  \nFor personal use only.  \nImmunoTargets and Therapy  \nOpen Access Full Text Article ORIGINAL RESEARCH  \nMachine Learning-Derived Neddylation Gene Signature for Predicting Prognosis and Immunotherapy Benefits in Colorectal Cancer  \nGuangda Yang 1 , *, Jieming Xiao2 , *, Huixiang He 3 , *, Jing Wang 1 , Zhichao Wang 1 , Liumeng Jian4 , Qianya Chen 1  \n1Department of Cancer Chemotherapy, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511300, People’s Republic of China; 2Department of Emergency, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511300, People’s Republic of China; 3Department of Laboratory Medicine, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511300, People’s Republic of  \nChina; 4Department of Neurology, the Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511300, People’s Republic of China *These authors contributed equally to this work  \nCorrespondence: Qianya Chen; Liumeng Jian, Email [chenqianya1987@163.com](chenqianya1987@163.com); [jinlium2012@163.com](jinlium2012@163.com)  \n\n| Background: Colorectal cancer (CRC) is a major cause of cancer deaths globally, mainly due to treatment resistance. Neddylation, a key post-translational modification, is linked to tumor growth and immune response, offering potential therapeutic targets, though its role in CRC is not well-explored.\u003Cbr>Methods: We examined neddylation-related genes (NRGs) across cell subtypes using CRC scRNA-seq data from the TISCH database. Unsupervised clustering of TCGA and GEO bulk RNA-seq data identified various neddylation patterns. A neddylationrelated gene signature (NRGS) was developed using ten machine-learning algorithms and validated externally. The study compared biofunctions, including functional analysis, immune cell infiltration, genomic mutations, enrichment analysis, and responses to immunotherapy and chemotherapy, between high-and low-risk groups defined by the NRGS model.\u003Cbr>Results: scRNA-seq analysis showed that the high neddylation score group had more malignant and diverse immune and stromal cells, with activated pathways aiding tumor growth and spread. We identified two neddylation patterns: Cluster A and Cluster B. Cluster B, associated with worse survival, had more immunosuppressive cells and increased tumor progression. We developed a neddylation-related gene signature (NRGS) using ten machine-learning algorithms, which accurately predicted outcomes. Higher risk scores correlated with poorer survival, with AUCs of 0.979, 0.989, and 0.996 for 1-year, 2-year, and 3-year OS in the training cohort. The NRGS was linked to higher recurrence or metastasis, advanced disease stage, and independently predicted OS risk. Patients with high NRGS may resist immunotherapy and standard chemotherapy.\u003Cbr>Conclusion: The NRGS could predict outcomes and responses to immunotherapy and chemotherapy in CRC patients, aiding personalized treatment, though further validation is needed.\u003Cbr>Keywords: colorectal cancer, CRC, neddylation, machine learning, prognosis, immunotherapy |\n| --- |\n| Introduction\u003Cbr>Colorectal cancer (CRC) is a major cause of cancer deaths globally, being the third most diagnosed and second deadliest cancer.1 Its poor prognosis is mainly due to treatment resistance. Despite advances in surgery, chemotherapy, and targeted therapies, survival rates for advanced CRC remain low.2 Immune checkpoint inhibitors (ICIs) like pembrolizumab and nivolumab show promise for metastatic CRC with mismatch-repair deficiency (dMMR) and high microsatellite instability (MSI-H), offering potential long-term remission for these patients.3 However, treating CRC with low immunogenicity, such as MSI-L/pMMR tumors, remains challenging. Current research aims to refine patient selection and develop new combination strategies to boost the effectiveness of ","cbCailEqO8Z72SYn","https://ap.wps.com/l/cbCailEqO8Z72SYn","pdf",30278576,1,22,"English","en",105,"# Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What biological and immune differences were observed between high- and low-risk groups?\",\"answer\":\"High neddylation score patients showed more malignant and diverse immune and stromal cells, with activated pathways related to tumor growth and spread. Two patterns were identified, where Cluster B—associated with poorer survival—contained more immunosuppressive cells and greater tumor progression.\"},{\"question\":\"What do the findings suggest about immunotherapy and chemotherapy response?\",\"answer\":\"Patients with high NRGS may resist immunotherapy and standard chemotherapy. The NRGS is also linked to features such as recurrence/metastasis and advanced disease stage while independently predicting OS risk.\"}]","Machine Learning-Derived Neddylation Gene Signature for Predicting Prognosis and Immunotherapy Benefits in Colorectal Cancer | PDF",1785676897,55,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":83,"head_meta":85,"extra_data":87,"updated_unix":28},"machine-learning-derived-neddylation-gene-signature-for-predicting-prognosis-and-immunotherapy-benefits-in-colorectal-cancer","",{"@graph":36,"@context":82},[37,54,69],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/research-report/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/machine-learning-derived-neddylation-gene-signature-for-predicting-prognosis-and-immunotherapy-benefits-in-colorectal-cancer/117546/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":63,"encodingFormat":61,"isAccessibleForFree":64,"interactionStatistic":65},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-08-05","2026-08-02",true,{"@type":66,"interactionType":67,"userInteractionCount":20},"InteractionCounter",{"@type":68},"ViewAction",{"@type":70,"mainEntity":71},"FAQPage",[72,78],{"name":73,"@type":74,"acceptedAnswer":75},"What biological and immune differences were observed between high- and low-risk groups?","Question",{"text":76,"@type":77},"High neddylation score patients showed more malignant and diverse immune and stromal cells, with activated pathways related to tumor growth and spread. Two patterns were identified, where Cluster B—associated with poorer survival—contained more immunosuppressive cells and greater tumor progression.","Answer",{"name":79,"@type":74,"acceptedAnswer":80},"What do the findings suggest about immunotherapy and chemotherapy response?",{"text":81,"@type":77},"Patients with high NRGS may resist immunotherapy and standard chemotherapy. The NRGS is also linked to features such as recurrence/metastasis and advanced disease stage while independently predicting OS risk.","https://schema.org",{"og:url":52,"og:type":84,"og:title":13,"og:site_name":59,"og:description":14},"article",{"robots":86,"canonical":52},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":89},[90,94,98,102,107,112,117,120,125,128,132],{"id":20,"doc_module":4,"doc_module_name":46,"category_name":91,"show_sort_weight":92,"slug":93},"Story & Novel",90,"story-novel",{"id":47,"doc_module":4,"doc_module_name":46,"category_name":95,"show_sort_weight":96,"slug":97},"Literature",80,"literature",{"id":53,"doc_module":4,"doc_module_name":46,"category_name":99,"show_sort_weight":100,"slug":101},"Exam",70,"exam",{"id":103,"doc_module":4,"doc_module_name":46,"category_name":104,"show_sort_weight":105,"slug":106},5,"Comic",60,"comic",{"id":108,"doc_module":4,"doc_module_name":46,"category_name":109,"show_sort_weight":110,"slug":111},6,"Technology",50,"technology",{"id":113,"doc_module":4,"doc_module_name":46,"category_name":114,"show_sort_weight":115,"slug":116},7,"Healthcare",40,"healthcare",{"id":11,"doc_module":4,"doc_module_name":46,"category_name":12,"show_sort_weight":118,"slug":119},30,"research-report",{"id":121,"doc_module":4,"doc_module_name":46,"category_name":122,"show_sort_weight":123,"slug":124},9,"Religion & Spirituality",20,"religion-spirituality",{"id":123,"doc_module":4,"doc_module_name":46,"category_name":126,"show_sort_weight":123,"slug":127},"World Cup","world-cup",{"id":129,"doc_module":4,"doc_module_name":46,"category_name":130,"show_sort_weight":129,"slug":131},10,"Lifestyle","lifestyle",{"id":133,"doc_module":4,"doc_module_name":46,"category_name":134,"show_sort_weight":103,"slug":135},19,"General","general"]