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Using TCGA and unsupervised clustering to define ccRCC molecular subgroups, the study characterized mutation patterns and immune microenvironments. A disulfidptosis-related prognostic score was built via LASSO-penalized Cox regression and validated in E-MATB-1980, yielding two sub-clusters with distinct survival and immunotherapy response profiles. Functional experiments implicated SLC7A11 in ccRCC metastasis.",{"@graph":69,"@context":127},[70,84,106],{"@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/a-new-perspective-deciphering-the-aberrance-and-clinical-implication-of-disulfidptosis-signatures-in-clear-cell-renal-cell-carcinoma/332182/",{"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/a-new-perspective-deciphering-the-aberrance-and-clinical-implication-of-disulfidptosis-signatures-in-clear-cell-renal-cell-carcinoma/332182.png","ImageObject",300,407,{"name":92,"@type":93},"Violet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What is the central goal of the study in ccRCC?","Question",{"text":113,"@type":114},"To clarify the clinical significance of disulfidptosis in clear cell renal cell carcinoma by defining ccRCC subgroups and building a prognostic signature tied to disulfidptosis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were ccRCC subgroups determined?",{"text":118,"@type":114},"The study used TCGA data and applied unsupervised clustering to assess ccRCC heterogeneity, then analyzed mutation landscapes and immune microenvironments across subgroups.",{"name":120,"@type":111,"acceptedAnswer":121},"How was the Disulfidptosis-Related Score developed and validated?",{"text":122,"@type":114},"A prognostic score was calculated using LASSO-penalized Cox regression, then validated in the E-MATB-1980 cohort using a 14-gene prognostic model.",{"name":124,"@type":111,"acceptedAnswer":125},"What experimental evidence links SLC7A11 to ccRCC progression?",{"text":126,"@type":114},"In vitro experiments including western blotting and Transwell assays identified SLC7A11 as a key participant in ccRCC metastasis, connecting gene regulation to functional outcomes.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},332182,1790012955,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":41,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149,"preview_page_count":4},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","[www.aging-us.com](www.aging-us.com) AGING 2024, Vol. 16, No. 11  \nResearch Paper  \nA new perspective: deciphering the aberrance and clinical implication of disulfidptosis signatures in clear cell renal cell carcinoma  \nBohong Chen1,*, Mingguo Zhou1,*, Li Guo1,*, Xinyue Sun2,*, Haoxiang Huang1, Kaijie Wu1, Wei Chen1, Dapeng Wu1  \n1 Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China 2 Department of neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China *Co-first author  \nCorrespondence to: Wei Chen, Dapeng Wu; email: [chenwei_urology@xjtufh.edu.cn](chenwei_urology@xjtufh.edu.cn), [wudapeng@xjtufh.edu.cn](wudapeng@xjtufh.edu.cn)[ ](wudapeng@xjtufh.edu.cn)[Keywords:](Keywords: disulfidptosis)[ disulfidptosis](Keywords: disulfidptosis), pan-cancer, clear cell renal cell carcinoma, molecular subtypes, single-cell RNA-seq  \nReceived: November 15, 2023 Accepted: May 3, 2024 Published: June 10, 2024  \nCopyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nABSTRACT  \nRecent research has discovered disulfidptosis as a form of programmed cell death characterized by disulfide stress. However, its significance in clear cell renal cell carcinoma (ccRCC) remains unclear. To investigate this, data from The Cancer Genome Atlas were collected and used to identify ccRCC subgroups. Unsupervised clustering was employed to determine ccRCC heterogeneity. The mutation landscape and immune microenvironment of the subgroups were analyzed. The Disulfidptosis-Related Score was calculated using the LASSO-penalized Cox regression algorithm. The E-MATB-1980 cohort was used to validate the signature. The role of SLC7A11 in ccRCC metastasis was explored using western blotting and Transwell assays. Disulfidptosisrelated genes are commonly downregulated in cancers and are linked to hypermethylation and copy number variation. The study revealed that ccRCC is divided into two sub-clusters: the disulfidptosis-desert sub-cluster, which is associated with a poor prognosis, a higher mutation frequency, and an immunosuppressive microenvironment. A 14-gene prognostic model was developed using differentially expressed genes and was validated in the E-MATB-1980 cohort. The low-risk group demonstrated longer overall and disease-free survival and responded better to targeted immunotherapy. Results from in vitro experiments identified SLC7A11 as a key participant in ccRCC metastasis.  \nINTRODUCTION  \nCancer is a leading cause of death worldwide, accounting for approximately 65% of all deaths [1] . As the human lifespan increases, the incidence and mortality of cancer also increase. Renal cell carcinoma (RCC) is a common malignancy of the genitourinary system. Clear cell RCC (ccRCC) accounts for approximately 75% of all RCC cases and is an aggressive subtype [2] . At the time of diagnosis, 20-30% of patients already have metastases. Even after surgical removal of the tumor, nearly 30% of the patients experience recurrence and metastasis [3, 4] .  \nFurthermore, advanced metastatic RCC shows a limited response to radiotherapy and chemotherapy, resulting in a restricted range of clinical treatment options and poor prognosis [5–7] . The 5-year survival rate of patients with metastatic renal cancer is less than 5%[8] . The TNM staging system is commonly used to predict kidney cancer prognosis. However, its predictive ability is limited because the survival rate can vary significantly among patients with the same stage of the disease [9] . Several prognostic models are available for predicting the outcomes of ccRCC. Bian et al. developed a predictive model for recurrence-free survival (RFS) in patients  \n10033  \nusing conventional clinical variables, such ","cbCaipHpnNyAfH3n","https://ap.wps.com/l/cbCaipHpnNyAfH3n","pdf",7197290,"English","# Abstract\n## Study design and datasets\n## Subgroup identification and microenvironment analysis\n## Prognostic signature construction and validation\n## Biomarker and functional validation (SLC7A11)\n# Introduction\n## Clinical burden and prognosis limits in ccRCC\n## Background: disulfidptosis and mechanism in cancer cells","[{\"question\":\"What is the central goal of the study in ccRCC?\",\"answer\":\"To clarify the clinical significance of disulfidptosis in clear cell renal cell carcinoma by defining ccRCC subgroups and building a prognostic signature tied to disulfidptosis.\"},{\"question\":\"How were ccRCC subgroups determined?\",\"answer\":\"The study used TCGA data and applied unsupervised clustering to assess ccRCC heterogeneity, then analyzed mutation landscapes and immune microenvironments across subgroups.\"},{\"question\":\"How was the Disulfidptosis-Related Score developed and validated?\",\"answer\":\"A prognostic score was calculated using LASSO-penalized Cox regression, then validated in the E-MATB-1980 cohort using a 14-gene prognostic model.\"},{\"question\":\"What experimental evidence links SLC7A11 to ccRCC progression?\",\"answer\":\"In vitro experiments including western blotting and Transwell assays identified SLC7A11 as a key participant in ccRCC metastasis, connecting gene regulation to functional outcomes.\"}]","A new perspective - deciphering the aberrance and clinical implication of disulfidptosis signatures in clear cell renal cell carcinoma | PDF",1789997224,76]