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This study investigates ferroptosis-related mechanisms and WDFY4 as potential immunotherapy targets by integrating Ferroptosis Index (FPI) analysis with immune infiltration, correlation statistics, and survival outcomes. Bioinformatic workflows include scRNA-seq clustering, pseudotime, single-cell GSVA, pathway enrichment, and core regulatory gene identification, followed by immunohistochemistry on LUAD tissue microarrays. Lentiviral WDFY4 transfection and multiple in vitro/in vivo assays validate effects on proliferation, apoptosis, migration, and tumor growth.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/ferroptosis-and-wdfy4-as-novel-targets-for-immunotherapy-of-lung-adenocarcinoma/377287/",{"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/ferroptosis-and-wdfy4-as-novel-targets-for-immunotherapy-of-lung-adenocarcinoma/377287.png","ImageObject",300,407,{"name":92,"@type":93},"Mabel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does ferroptosis-related activity (FPI) play in LUAD patient survival?","Question",{"text":112,"@type":113},"Survival analysis shows that smaller FPI values are positively associated with longer overall survival in LUAD patients. Immune infiltration patterns are also related to FPI.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which immune cell type is most strongly linked to ferroptosis in this study?",{"text":117,"@type":113},"B cells show the strongest association with ferroptosis. Greater B cell infiltration and activation correlate with longer long-term survival.",{"name":119,"@type":110,"acceptedAnswer":120},"How does WDFY4 affect LUAD biology and therapeutic potential?",{"text":121,"@type":113},"WDFY4 is implicated in regulating B cell differentiation in LUAD, with low WDFY4 expression linked to poorer prognosis. Overexpression suppresses proliferation and metastasis of A549 cells and inhibits tumor growth in vivo.","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},377287,1790828854,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},7971474920318,"https://ap-avatar.wpscdn.com/avatar/74000ee537e6b0ca360?x-image-process=image/resize,m_fixed,w_180,h_180&k=1788430171632181674","[www.aging-us.com](www.aging-us.com) AGING 2023, Vol. 15, No. 18  \nResearch Paper  \nFerroptosis and WDFY4 as novel targets for immunotherapy of lung adenocarcinoma  \nLing Huang1,2,3,*, Lifan Zhong3,*, Ruxin Cheng4,*, Limei Chang2, Mingyan Qin2, Huaping Liang 1, Zhongkai Liao5  \n1State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Daping Hospital, Army Medical University, Chongqing, China  \n2 Hainan Center for Drug and Medical Device Evaluation and Service, Hainan Medical Products Administration, Haikou, China  \n3School of Hainan Provincial Drug Safety Evaluation Research Center, Hainan Medical University, Haikou, China 4 Emergency and Trauma College, Hainan Medical University, Haikou, Hainan, China  \n5 Department of Thoracic Surgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, China  \n* Equal contribution  \nCorrespondence to: Zhongkai Liao, Huaping Liang; email: [liaozhongkai@shhmu.net](liaozhongkai@shhmu.net); [13638356728@163.com](13638356728@163.com), [https://orcid.org/0000-0003-4157-445X](https://orcid.org/0000-0003-4157-445X)  \nKeywords: Single Cell RNA-Sequencing, lung adenocarcinoma, WDFY4, immunotherapy, ferroptosis  \nReceived: February 22, 2023 Accepted: August 21, 2023 Published: September 19, 2023  \nCopyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nABSTRACT  \nBackground: Lung cancer exhibits the world’s highest mortality rate among malignant cancers worldwide, thereby presenting a significant global challenge in terms of reducing patient mortality. In the field of oncology, targeted immunotherapy has emerged as a novel therapeutic approach for lung cancer. This study aims to explore potential targets for immunotherapy in lung adenocarcinoma (LUAD) through the analysis of Ferroptosis Index (FPI) and Single Cell RNA-Sequencing (scRNA-seq) data. The findings of this research can potentially offer valuable insights for improving LUAD immunotherapy strategies and informing clinical decision-making.  \nMethods: Firstly, the relationship between survival and ferroptosis in LUAD patients was analyzed by FPI. Subsequently, the association between ferroptosis and infiltration and regulation of immune cells was explored by immune infiltration analysis and correlation statistics. Lastly, the relationship between major infiltrating immune cell populations and related pathways and prognosis of LUAD patients was analyzed by GSEA and GSVA. To screen out core genes regulating infiltration of immune cell populations, scRNA-seq data of cancer and para-cancerous tissues of LUAD patients were downloaded, followed by cell clustering analysis, cell identification of core subpopulations, pseudotime analysis, single-cell GSVA and pathway enrichment analysis, and identification and functional analysis of core regulatory genes. Moreover, the expression levels of core functional genes in LUAD tissue microarray were detected by immunohistochemistry, and its relationship with the prognosis of LUAD patients was verified. Finally, we used lentivirus with WDFY4 to transfect LUAD A549 cells. CCK-8, flow cytometry apoptosis detection, Scratch wound healing assay, Transwell migration assay, Xenograft nude mice model, immunohistochemical analysis and other experimental methods were used to explore the biological effects of WDFY4 on LUAD in vitro and in vivo.  \nResults: Survival analysis of FPI values in LUAD patients revealed a positive correlation between smaller FPI values and longer overall survival. Immuno-infiltration analysis and its correlation with FPI values revealed that  \nB cells were most strongly associated with ferroptosis. Ferroptosis of cancer cells could promote infiltration and activation of B cell populations, and LUAD patients with mor","cbCaiklS7TnPvsYF","https://ap.wps.com/l/cbCaiklS7TnPvsYF","pdf",2575771,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What role does ferroptosis-related activity (FPI) play in LUAD patient survival?\",\"answer\":\"Survival analysis shows that smaller FPI values are positively associated with longer overall survival in LUAD patients. Immune infiltration patterns are also related to FPI.\"},{\"question\":\"Which immune cell type is most strongly linked to ferroptosis in this study?\",\"answer\":\"B cells show the strongest association with ferroptosis. Greater B cell infiltration and activation correlate with longer long-term survival.\"},{\"question\":\"How does WDFY4 affect LUAD biology and therapeutic potential?\",\"answer\":\"WDFY4 is implicated in regulating B cell differentiation in LUAD, with low WDFY4 expression linked to poorer prognosis. Overexpression suppresses proliferation and metastasis of A549 cells and inhibits tumor growth in vivo.\"}]","Ferroptosis and WDFY4 as novel targets for immunotherapy of lung adenocarcinoma | PDF",1790224115,48]