{"title":"Genetic Distinctiveness in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Cancer: Identifying Key Genomic Signatures through Differentially Expressed Gene Analysis.","authors":"Patrick Shi, Wenqiang Chen","doi":"10.2174/0115680096372957250322174718","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most commonly diagnosed cancer type and the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer cases and includes two main subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Understanding the differences in genes causing the proliferation of LUAD and LUSC is key to advancing the diagnosis and targeted treatment development.</p><p><strong>Aims: </strong>The aim of this study was to identify candidate genes and potential tumorigenesis mechanisms distinguishing LUAD and LUSC.</p><p><strong>Methods: </strong>Three pooled transcriptomic datasets (GSE10245, GSE37745, and GSE43580) were analyzed from the Gene Expression Omnibus (GEO) database, with each dataset statistically tested for differentially expressed genes (DEGs). DEGs between lung LUAD and LUSC of the three datasets were analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed to screen candidate genes.</p><p><strong>Results: </strong>This study identified 138 shared DEGs among three patient-level gene expression datasets, containing 39 upregulated genes and 99 downregulated genes. The GO and KEGG enrichment analysis results showed the functions of DEGs to be mainly associated with epidermis development, cornified envelope, structural constituent of epidermis, and estrogen signaling pathway. Finally, through the PPI network, eight core genes were identified, including KRT14, KRT5, KRT6A, KRT16, SPRR1A, SPRR1B, SPRR3, and KRT6B.</p><p><strong>Conclusion: </strong>We have elucidated key genes and molecular mechanisms linked to NSCLC subtypes. These findings have the potential to facilitate improved diagnostic and therapeutic targets for LUAD and LUSC biomarkers.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current cancer drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680096372957250322174718","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Lung cancer is the most commonly diagnosed cancer type and the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer cases and includes two main subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Understanding the differences in genes causing the proliferation of LUAD and LUSC is key to advancing the diagnosis and targeted treatment development.
Aims: The aim of this study was to identify candidate genes and potential tumorigenesis mechanisms distinguishing LUAD and LUSC.
Methods: Three pooled transcriptomic datasets (GSE10245, GSE37745, and GSE43580) were analyzed from the Gene Expression Omnibus (GEO) database, with each dataset statistically tested for differentially expressed genes (DEGs). DEGs between lung LUAD and LUSC of the three datasets were analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed to screen candidate genes.
Results: This study identified 138 shared DEGs among three patient-level gene expression datasets, containing 39 upregulated genes and 99 downregulated genes. The GO and KEGG enrichment analysis results showed the functions of DEGs to be mainly associated with epidermis development, cornified envelope, structural constituent of epidermis, and estrogen signaling pathway. Finally, through the PPI network, eight core genes were identified, including KRT14, KRT5, KRT6A, KRT16, SPRR1A, SPRR1B, SPRR3, and KRT6B.
Conclusion: We have elucidated key genes and molecular mechanisms linked to NSCLC subtypes. These findings have the potential to facilitate improved diagnostic and therapeutic targets for LUAD and LUSC biomarkers.
背景：肺癌是世界上最常见的癌症类型，也是癌症死亡的主要原因。非小细胞肺癌（NSCLC）占所有肺癌病例的80%以上，包括两个主要亚型：肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）。了解导致LUAD和LUSC增殖的基因差异是推进诊断和靶向治疗发展的关键。目的：本研究的目的是鉴定区分LUAD和LUSC的候选基因和潜在的肿瘤发生机制。方法：从Gene Expression Omnibus （GEO）数据库中对三个转录组数据集（GSE10245、GSE37745和GSE43580）进行分析，并对每个数据集进行差异表达基因（DEGs）的统计检验。利用基因本体（GO）和京都基因与基因组百科全书（KEGG）途径富集分析三个数据集的肺LUAD和LUSC之间的deg。构建蛋白-蛋白相互作用（PPI）网络筛选候选基因。结果：本研究在三个患者水平的基因表达数据集中鉴定出138个共有的deg，其中39个基因上调，99个基因下调。GO和KEGG富集分析结果表明，DEGs的功能主要与表皮发育、角质包膜、表皮结构成分和雌激素信号通路有关。最后，通过PPI网络鉴定出8个核心基因，包括KRT14、KRT5、KRT6A、KRT16、SPRR1A、SPRR1B、SPRR3和KRT6B。结论：我们已经阐明了与NSCLC亚型相关的关键基因和分子机制。这些发现有可能促进改善LUAD和LUSC生物标志物的诊断和治疗靶点。
期刊介绍：
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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