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The study identifies DNA-methylation-driven genes linked to prognosis in lung squamous cell carcinoma (LUSC) to support targeted therapy discovery. Methylation and RNA-seq datasets from TCGA, integrated with MethylMix and validated using GEO GSE37745, yield 45 MDGs, with ALDH7A1 associated with survival, high-risk scores, and methylation-dependent expression and pathway activation. Experimental knockdown and overexpression confirm functional effects on tumor progression.",{"@graph":69,"@context":126},[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/identification-of-aldh7a1-as-a-dna-methylation-driven-gene-in-lung-squamous-cell-carcinoma/340756/",{"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/identification-of-aldh7a1-as-a-dna-methylation-driven-gene-in-lung-squamous-cell-carcinoma/340756.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What data sources and analytical tools were used to identify methylation-driven genes in LUSC?","Question",{"text":112,"@type":113},"Methylation and RNA-seq data were downloaded from TCGA and integrated using the MethylMix package. The LUSC dataset GSE37745 from GEO was used for validation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is ALDH7A1 linked to prognosis in lung squamous cell carcinoma?",{"text":117,"@type":113},"ALDH7A1 high expression was significantly associated with poorer survival and was identified as an independent risk factor. A risk model and Kaplan–Meier analysis showed worse outcomes for high-risk scores.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the relationship between ALDH7A1 expression and its DNA methylation status?",{"text":121,"@type":113},"ALDH7A1 expression is negatively correlated with its methylation status (correlation coefficient given as cOR = −0.655).",{"name":123,"@type":110,"acceptedAnswer":124},"How did pathway enrichment and cell experiments support the role of ALDH7A1?",{"text":125,"@type":113},"GSEA indicated that high ALDH7A1 expression activates pathways including JAK-STAT and mTOR. In vitro experiments showed that ALDH7A1 silencing inhibits tumor progression, while overexpression promotes progression in LUSC.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},340756,1790806495,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"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},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","AnnAls of Medicine  \n2025, Vol. 57, no. 1, 2442529  \n[https://doi.org/10.1080/07853890.2024.2442529](https://doi.org/10.1080/07853890.2024.2442529)  \nReseaRch aRticle    \nIdentification of ALDH7A1 as a DNA-methylation-driven gene in lungsquamous cell carcinoma  \nGaofeng lianga, Jinxian hea, tian chenb, liang Zhangc, Kaizhong Yua and Weiyu shena  \nadepartment of Thoracic surgery, The Affiliated liHuili Hospital of ningbo University, ningbo, Zhejiang, china; bdepartment of Radiation oncology, The Affiliated liHuili Hospital of ningbo University, ningbo, Zhejiang, chinaccdepartment of Respiratory Medicine, The Affiliated liHuili Hospital of ningbo University, ningbo, Zhejiang, china  \nABSTRACT  \nBackground: Deoxyribose nucleic acid (DNa) methylation is an important epigenetic modification that plays an important role in the occurrence and development of tumors. identifying key methylation-driven genes that affect the prognosis of lung squamous cell carcinoma (lUsc) can provide direction for targeted therapy research.  \nMethods and results: Methylation and RNa-seq data were downloaded from the cancer Genome atlas (tcGa). the MethylMix package was used to integrate and analyze the methylation and gene expression data from tcGa, and the lUsc dataset (Gse37745) was downloaded from GeO for validation. Forty-five DNa-methylation-driven genes (MDGs) were obtained, and 3 genes (tRiM61, sMiM22, and alDh7a1) were significantly associated with survival by using univariate and multivariate cox regression. a risk model was constructed. KM analysis showed that patients with high-risk scores had poor survival. a nomination plot for prognosis prediction of lUsc patients was constructed, which showed a good predictive efficiency for tumor prognosis. the high expression of alDh7a1 was an independent risk factor for poor prognosis in lUsc. the expression of alDh7a1 in lUsc was negatively correlated with its methylation status (cOR = −0.655). Gsea analysis showed that high expression of alDh7a1 could activate multiple signaling pathways (JaK-stat signaling pathway and mtOR signaling pathway). In vitro cell experiments confirmed that in lUsc, silencing alDh7a1 could inhibit tumor progression, while overexpression of alDh7a1 could promote tumor progression.  \nConclusion: Our results indicated that alDh7a1, a newly discovered MDG in lUsc, could act asan independent prognostic factor for Os in lUsc, with the potential to become a potential target for lUsc diagnosis and treatment. high expression of alDh7a1 in lUsc could promote the occurrence and development of tumors. signaling pathways, such as JaK-stat and mtOR signaling pathways, might regulate the high expression of alDh7a1.  \nARTICLE HISTORY  \nReceived 16 January 2024 Revised 17 October 2024 accepted 29 October 2024  \nKEYWORDS  \nlung squamous cell carcinoma; DNa methylation; survival analysis; methylation driver gene; alDh7a  \nIntroduction  \nlung squamous cell carcinomas (lUsc) are a distinct histologic subtype of Nsclc, accounting for ~25–30% of all Nsclc cases. the early symptoms of lUsc are not obvious, leading to its insidious nature, and patients are often older or have advanced disease atthe time of diagnosis [1] . in recent years, the application of programmed death-1 (PD-1)/programmed death ligand 1 (PD-l1) inhibitors for the treatment of Nsclc patients has made great progress, with several  \nbenefits, especially for patients with early-stage disease [2,3] . since most lUsc patients were diagnosed atan advanced stage, systemic treatment options are limited, and disease-related mortality is high. even with the addition of PD-(l)1 inhibitors, the median Os for lUsc patients receiving first-line combination immunotherapy and chemotherapy is only 17.1 months [4] . therefore, finding effective biomarkers for early identification is an important preventive measure to improve the prognosis of patients with lUsc.  \nCONTACT Kaizhong Yu  [82531975@qq.com](82531975@qq.com)  department of Thoracic sur","cbCaitjfaVrAHbOI","https://ap.wps.com/l/cbCaitjfaVrAHbOI","pdf",16559626,17,"English","# Abstract\n# Introduction\n## DNA methylation in tumors\n# Methods and results\n## Identification of methylation-driven genes\n## Prognostic risk model and validation\n## ALDH7A1 methylation-expression relationship\n## Pathway analysis and functional validation","[{\"question\":\"What data sources and analytical tools were used to identify methylation-driven genes in LUSC?\",\"answer\":\"Methylation and RNA-seq data were downloaded from TCGA and integrated using the MethylMix package. The LUSC dataset GSE37745 from GEO was used for validation.\"},{\"question\":\"How is ALDH7A1 linked to prognosis in lung squamous cell carcinoma?\",\"answer\":\"ALDH7A1 high expression was significantly associated with poorer survival and was identified as an independent risk factor. A risk model and Kaplan–Meier analysis showed worse outcomes for high-risk scores.\"},{\"question\":\"What is the relationship between ALDH7A1 expression and its DNA methylation status?\",\"answer\":\"ALDH7A1 expression is negatively correlated with its methylation status (correlation coefficient given as cOR = −0.655).\"},{\"question\":\"How did pathway enrichment and cell experiments support the role of ALDH7A1?\",\"answer\":\"GSEA indicated that high ALDH7A1 expression activates pathways including JAK-STAT and mTOR. In vitro experiments showed that ALDH7A1 silencing inhibits tumor progression, while overexpression promotes progression in LUSC.\"}]","Identification of ALDH7A1 as a DNA-methylation-driven gene in lung squamous cell carcinoma | PDF",1790038716,43]