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Single-cell transcriptomics enables detailed profiling of cellular and molecular heterogeneity, clarifying tumor microenvironment dynamics. This study investigates STAT1 and its regulatory relationship with the tumor suppressor LHPP, linking transcriptional control to ESCC progression and therapeutic implications. Single-cell GEO data and validation in patient cohorts and ESCC cell models define STAT1 as a core regulator of LHPP expression, with promoter-level repression.",{"@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/single-cell-transcriptomics-reveals-stat1-drives-lhpp-downregulation-in-esophageal-squamous-cell-carcinoma-progression-research-article/329321/",{"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/single-cell-transcriptomics-reveals-stat1-drives-lhpp-downregulation-in-esophageal-squamous-cell-carcinoma-progression-research-article/329321.png","ImageObject",300,407,{"name":92,"@type":93},"Eden","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of this study in ESCC?","Question",{"text":112,"@type":113},"The study focuses on how the transcription factor STAT1 regulates the tumor suppressor LHPP and how this relationship contributes to ESCC progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What data and validation strategies were used?",{"text":117,"@type":113},"Single-cell transcriptomics data were obtained from the public GEO database (GSE160269). Findings were further validated using a cohort of 21 ESCC patients and transcriptional relationship experiments in ESCC cell lines.",{"name":119,"@type":110,"acceptedAnswer":120},"How did STAT1 and LHPP expression relate in patient samples?",{"text":121,"@type":113},"Patient samples showed elevated STAT1 and reduced LHPP expression. STAT1 negatively regulates LHPP at the promoter level, and mutating promoter binding motif regions weakened LHPP transcriptional repression.","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},329321,1790129870,{"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":39,"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},1374391974468,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Single-Cell Transcriptomics Reveals STAT1 Drives LHPP Downregulation in Esophageal Squamous Cell Carcinoma Progression  \nXia Chen 1 , Zhiyun Xu2, Wubi Zhou 1, Lili Zhang 1, Jian Huang 1, and Dawei Bao 1  \nTechnology in Cancer Research & Treatment  \nVolume 23: 1-13  \n© The Author(s) 2024  \nArticle reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI: 10.1177/15330338241293485](DOI: 10.1177/15330338241293485)[ ](DOI: 10.1177/15330338241293485)[journals.sagepub.com/home/tct](journals.sagepub.com/home/tct)  \nAbstract  \nBackground: Esophageal Squamous Cell Carcinoma (ESCC) poses a signiﬁcant health challenge in China due to its high incidence and mortality. Single-cell transcriptomics has transformed the approach to cancer research, allowing detailed analysis of cellular and molecular heterogeneity. The interaction between the transcription factor STAT1 and the tumor suppressor LHPP is crucial, potentially inﬂuencing cancer progression and therapeutic outcomes. Objective: This study aims to explore the molecular mechanisms and cellular dynamics underlying ESCC, with a focus on the role of transcription factors, particularly STAT1, and its regulatory relationship with LHPP, in the pathogenesis of ESCC. Methods: Utilizing single-cell transcriptomics data sourced from the public database GEO (GSE160269), we identiﬁed major cell types and their transcriptomic changes in ESCC patients. Differential gene expression proﬁles were examined to understand the dynamics of the tumor microenvironment (TME). A cohort of 21 ESCC patients was recruited to validate the ﬁndings. Furthermore, in ESCC cell lines, we validated the transcriptional regulatory relationship between STAT1 and LHPP. Results: Our analysis identiﬁed six major cell types within the ESCC microenvironment, revealing signiﬁcant changes in cellular composition and gene expression proﬁles associated with tumorigenesis. Notably, a novel association between STAT1’s regulatory role over LHPP was observed, suggesting a complex regulatory loop in ESCC pathogenesis. Elevated STAT1 and reduced LHPP expression were conﬁrmed in patient samples with STAT1 negatively regulates LHPP expression at the promoter level; when the promoter binding motif regions were mutated, the transcriptional repression ability on LHPP was weakened. Conclusion: The study highlights STAT1 as a core regulator in ESCC, directly inﬂuencing LHPP expression. The ﬁndings offer novel insights into the molecular mechanisms driving ESCC, shedding light on the cellular alterations and gene regulation dynamics within the ESCC microenvironment. This research provides a foundation for developing targeted therapeutic strategies, potentially utilizing the STAT1-LHPP axis as a focal point in ESCC treatment and prognosis.  \nKeywords  \nesophageal squamous cell carcinoma, single-cell trascriptomics, tumor microenvironment, signal transducer and activator of transcription 1  \nReceived: June 27, 2024; Revised: September 9, 2024; Accepted: September 20, 2024.  \nIntroduction  \nEsophageal squamous cell carcinoma (ESCC) stands as one of the foremost malignancies both globally and in China.1–3 Globally, ESCC accounts for a signiﬁcant portion of cancerrelated deaths, with its prognosis remaining grim due to late diagnosis and limited treatment options.4 Meanwhile, China confronts an even more exacerbated burden. The nation harbors a substantial fraction of ESCC cases, making it a primary public health concern.5 A combination of genetic predisposition, environmental factors, and dietary habits have contributed to its elevated prevalence in the Chinese demographic.6,7  \nTo unravel the underlying complexities of cancers like ESCC, researchers have turned to sophisticated cancer databases. The inception of single-cell transcriptomics is  \n1 Department of Pathology, The Afﬁliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an, China  \n2 Department of T","cbCainH4zd1WzYZk","https://ap.wps.com/l/cbCainH4zd1WzYZk","pdf",3506727,13,"English","# Abstract\n## Background\n## Objective\n## Methods\n## Results\n## Conclusion\n# Introduction\n## ESCC burden and risk factors\n## Why single-cell transcriptomics\n## Transcription factors and STAT1","[{\"question\":\"What is the main focus of this study in ESCC?\",\"answer\":\"The study focuses on how the transcription factor STAT1 regulates the tumor suppressor LHPP and how this relationship contributes to ESCC progression.\"},{\"question\":\"What data and validation strategies were used?\",\"answer\":\"Single-cell transcriptomics data were obtained from the public GEO database (GSE160269). Findings were further validated using a cohort of 21 ESCC patients and transcriptional relationship experiments in ESCC cell lines.\"},{\"question\":\"How did STAT1 and LHPP expression relate in patient samples?\",\"answer\":\"Patient samples showed elevated STAT1 and reduced LHPP expression. STAT1 negatively regulates LHPP at the promoter level, and mutating promoter binding motif regions weakened LHPP transcriptional repression.\"}]","Single-Cell Transcriptomics Reveals STAT1 Drives LHPP Downregulation in Esophageal Squamous Cell Carcinoma Progression - Research Article | PDF",1789983667,33]