[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332314-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332314-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","gene-regulatory-networks-reveal-sex-difference-in-lung-adenocarcinoma-research-open-access","Gene regulatory networks reveal sex difference in lung adenocarcinoma - Research Open Access","","Lung adenocarcinoma shows pronounced sex differences in incidence, prognosis, and therapeutic response, yet the underlying molecular drivers remain insufficiently explored. This study uses sample-specific gene regulatory network approaches on RNA-seq data from non-cancer lung tissue (GTEx) and primary tumors (TCGA), validating findings in independent datasets. Results identify sex-differential regulation across key pathways, modulated by tobacco smoking, and sex-biased transcription factor targeting of actionable oncogenes and tumor suppressors, including AKT2 and KRAS.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/gene-regulatory-networks-reveal-sex-difference-in-lung-adenocarcinoma-research-open-access/332314/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/gene-regulatory-networks-reveal-sex-difference-in-lung-adenocarcinoma-research-open-access/332314.png","ImageObject",300,407,{"name":42,"@type":43},"Liam","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What data sources were used to study sex differences in lung adenocarcinoma?","Question",{"text":63,"@type":64},"The study analyzed RNA sequencing data from non-cancerous lung samples from GTEx and lung adenocarcinoma primary tumor samples from TCGA, with results validated using independent data.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which biological pathways show sex-differential gene regulatory activity?",{"text":68,"@type":64},"Genes linked to cell proliferation, immune response, and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumors.",{"name":70,"@type":61,"acceptedAnswer":71},"How does smoking history influence the observed sex differences?",{"text":72,"@type":64},"The regulatory differences between males and females are further perturbed by tobacco smoking, indicating smoking modifies the sex-associated gene regulation patterns.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},332314,1790494945,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":127,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144,"preview_page_count":4},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Saha et al. Biology of Sex Differences (2024) 15:62 [https://doi.org/10.1186/s13293-024-00634-y](https://doi.org/10.1186/s13293-024-00634-y)  \nBiology of Sex Differences  \n RESEARCH Open Access  \nGene regulatory networks reveal sex difference in lung adenocarcinoma  \nEnakshi Saha1, Marouen Ben Guebila1, Viola Fanfani 1, Jonas Fischer 1, Katherine H. Shutta 1,2,  \nPanagiotis Mandros1, Dawn L. DeMeo2,3, John Quackenbush1,2,4 and Camila M. Lopes‑Ramos 1,2,3*  \nAbstract  \nBackground Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prog‑ nosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively.  \nMethods Sample‑specific gene regulatory network methods were used to analyze RNA sequencing data from non‑ cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data.  \nResults We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small‑molecule drugs that might have sex‑biased efficacy as can‑ cer therapeutics and further validated this observation using an independent cell line database.  \nConclusions These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.  \nHighlights  \n• Genes associated with cell proliferation, immune response, and drug metabolism are differentially targeted by transcription factors between males and females in healthy lung tissue and lung adenocarcinoma samples.  \n• Gene regulatory differences between males and females are also affected by an individual’s history of smoking.  \n• Significant sex bias exists in transcription factor targeting patterns of several clinically actionable oncogenesand tumor suppressor genes including AKT2 and KRAS.  \n• Analyzing sex‑biased gene regulatory networks in lung adenocarcinoma identified small‑molecule cancer thera‑ peutics with potential sex‑specific efficacy, underscoring the importance of considering sex‑specific gene regula‑ tion in precision medicine.  \n*Correspondence:  \nCamila M. Lopes‑Ramos  \n[nhclr@channing.harvard.edu](nhclr@channing.harvard.edu)  \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 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. 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/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiv","cbCaivoWwHENgUKb","https://ap.wps.com/l/cbCaivoWwHENgUKb","pdf",3725864,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Plain English Summary\n# Graphical Abstract\n# Introduction","[{\"question\":\"What data sources were used to study sex differences in lung adenocarcinoma?\",\"answer\":\"The study analyzed RNA sequencing data from non-cancerous lung samples from GTEx and lung adenocarcinoma primary tumor samples from TCGA, with results validated using independent data.\"},{\"question\":\"Which biological pathways show sex-differential gene regulatory activity?\",\"answer\":\"Genes linked to cell proliferation, immune response, and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumors.\"},{\"question\":\"How does smoking history influence the observed sex differences?\",\"answer\":\"The regulatory differences between males and females are further perturbed by tobacco smoking, indicating smoking modifies the sex-associated gene regulation patterns.\"}]","Gene regulatory networks reveal sex difference in lung adenocarcinoma - Research Open Access | PDF",1789997678,48]