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Digital spatial profiling, CosMx single-cell spatial transcriptomics, and immunohistochemical analysis were applied to early-stage ESCC across histologic regions, alongside public bulk and scRNA-seq datasets and functional experiments. Spatial reprogramming and dynamic signaling revealed macrophage infiltration across dysplasia-to-cancer stages. Cell–cell communication suggested MIF-CD74 protumor interactions, and DTX3L/BST2 expression rose with progression. Functional assays showed DTX3L or BST2 knockdown suppresses proliferation, migration, and M2 polarization.",{"@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/spatial-transcriptome-profiling-identifies-dtx3l-and-bst2-as-key-biomarkers-in-esophageal-squamous-cell-carcinoma-tumorigenesis/329659/",{"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/spatial-transcriptome-profiling-identifies-dtx3l-and-bst2-as-key-biomarkers-in-esophageal-squamous-cell-carcinoma-tumorigenesis/329659.png","ImageObject",300,407,{"name":92,"@type":93},"Clementine","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",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 molecular changes were tracked during ESCC progression?","Question",{"text":112,"@type":113},"The study examined transcriptional alterations and immunologic changes across normal tissue, low-/high-grade dysplasia, and cancerous regions using spatial profiling approaches.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were macrophages characterized and what trend was observed?",{"text":117,"@type":113},"Macrophages increased from normal tissues through dysplasia to cancerous tissues, and macrophage subtypes were characterized using scRNA-seq data.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biomarkers were implicated and what did functional tests show?",{"text":121,"@type":113},"DTX3L and BST2 emerged as key biomarkers, with their knockdown inhibiting ESCC proliferation and migration and reducing M2 polarization of tumor-associated macrophages.","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},329659,1790690592,{"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":34,"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},1374391974564,"https://ap-avatar.wpscdn.com/avatar/14000253aa45c000a9e?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779874745381141002","Li etal. Genome Medicine (2024) 16:148 [https://doi.org/10.1186/s13073-024-01422-4](https://doi.org/10.1186/s13073-024-01422-4)  \nGenome Medicine  \n RESEARCH Open Access  \nSpatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis  \nRutao Li1,2,3†, Na Li4*†, Qianqian Yang5†, Xing Tong5†, Wei Wang4†, Chang Li1,2, Jun Zhao1,2, Dong Jiang1,2, Haitao Huang1,2, Chen Fang3, Kai Xie3, Jiamin Yuan6, Shaomu Chen1,2, Guangbin Li 1,2, Haitao Luo4, Zhibo Gao4, Dongfang Wu4, Xiaoli Cui4, Wei Jiang3, Lingchuan Guo5*, Haitao Ma1,3* andYu Feng1,2*  \nAbstract  \nBackground Understanding the stepwise progression of esophageal squamous cell carcinoma (ESCC) is cru  \ncial for developing customized strategies for early detection and optimal clinical management. Herein, we aimed to unravel the transcriptional and immunologic alterations occurring during malignant transformation and identify clinically significant biomarkers of ESCC.  \nMethods Digital spatial profiling (DSP) was performed on 11 patients with early-stage ESCC (pT1) to explore the transcriptional alterations in epithelial, immune cell, and non-immune cell stromal compartments across regions of distinct histology, including normal tissues, low-and high-grade dysplasia, and cancerous tissues. Furthermore, singlecell spatial transcriptomics was performed using the CosMx Spatial Molecular Imaging (SMI) system on 4 additional patients with pT1 ESCC. Immunohistochemical (IHC) analysis was performed on consecutive histological sections of 20 pT1 ESCCs. Additionally, public bulk and single-cell RNA-sequencing (scRNA-seq) datasets were analyzed, and in vitro and in vivo functional studies were conducted.  \nResults Spatial transcriptional reprogramming and dynamic cell signaling pathways that determined ESCC progression were delineated. Increased infiltration of macrophages from normal tissues through dysplasia to cancerous tissues occurred. Macrophage subtypes were characterized using the scRNA-seq dataset. Cell–cell communication analysis of scRNA-seq and SMI data indicated that the migration inhibitory factor (MIF)-CD74 axis may exhibit protumor interactions between macrophages and epithelial cells. DSP, SMI, and IHC data demonstrated that DTX3L  \n†Rutao Li, Na Li, QianqianYang, Xing Tong and Wei Wang contributed equally to this work.  \n*Correspondence:  \nNa Li[lina574359748@gmail.com](lina574359748@gmail.com)[ ](lina574359748@gmail.com)Lingchuan Guo [szglc@hotmail.com](szglc@hotmail.com)[ ](szglc@hotmail.com)Haitao Ma[mht7403@163.com](mht7403@163.com)[ ](mht7403@163.com)Yu Feng [fengyu1@suda.edu.cn](fengyu1@suda.edu.cn)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.)  \nLi etal. Genome Medicine (2024) 16:148 Page 2 of 22  \nexpression in epithelial cells and BST2 expre","cbCaig1HzYVBXGHI","https://ap.wps.com/l/cbCaig1HzYVBXGHI","pdf",12841988,22,"English","## Background\n## Methods\n## Results\n## Conclusions\n## Keywords","[{\"question\":\"What molecular changes were tracked during ESCC progression?\",\"answer\":\"The study examined transcriptional alterations and immunologic changes across normal tissue, low-/high-grade dysplasia, and cancerous regions using spatial profiling approaches.\"},{\"question\":\"How were macrophages characterized and what trend was observed?\",\"answer\":\"Macrophages increased from normal tissues through dysplasia to cancerous tissues, and macrophage subtypes were characterized using scRNA-seq data.\"},{\"question\":\"Which biomarkers were implicated and what did functional tests show?\",\"answer\":\"DTX3L and BST2 emerged as key biomarkers, with their knockdown inhibiting ESCC proliferation and migration and reducing M2 polarization of tumor-associated macrophages.\"}]","Spatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis | PDF",1789985093,55]