Premalignant lesions within the bronchial epithelium signify the initial phases of squamous cell lung carcinoma, posing challenges for detection via conventional methods. Instead of focusing solely on gene expression, in this study, we explore transcriptomic alterations linked to lesion progression, with an emphasis on protein-coding transcripts. We reanalyzed a publicly available RNA-Seq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript and gene abundance were quantified using kallisto, while differential expression and transcript usage analysis was performed utilizing sleuth and RATs packages. Functional characterization involved overrepresentation analysis via clusterProfiler, weighted coexpression network analysis (WGCNA), and network analysis via Enrichr-KG. We detected 5906 differentially expressed transcripts and 4626 genes, exhibiting significant enrichment within pathways associated with oxidative phosphorylation and mitochondrial function. Remarkably, transcript-level WGCNA revealed a single module correlated with dysplasia status, notably enriched in cilium-related biological processes. Notable hub transcripts included RABL2B (ENST00000395590), DNAH1 (ENST00000420323), EFHC1 (ENST00000635996), and VWA3A (ENST00000563389) along with transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant bronchial lesion biology, including identification of potential biomarkers associated with early lung carcinogenesis.
支气管上皮内的癌前病变是肺鳞状细胞癌的初始阶段，通过常规方法检测存在挑战。本研究不仅关注基因表达，更深入探索与病变进展相关的转录组学改变，重点聚焦于蛋白质编码转录本。我们重新分析了公开可用的RNA-Seq数据集，该数据集包含82名吸烟者的气道上皮细胞样本，其中部分存在癌前病变。使用kallisto对转录本和基因丰度进行定量，同时利用sleuth和RATs软件包进行差异表达及转录本使用模式分析。功能表征包括通过clusterProfiler进行过表达分析、加权共表达网络分析（WGCNA）以及通过Enrichr-KG进行网络分析。我们检测到5906个差异表达转录本和4626个基因，这些在氧化磷酸化和线粒体功能相关通路中显著富集。值得注意的是，转录本水平的WGCNA揭示了一个与发育异常状态相关的独立模块，该模块在纤毛相关生物过程中显著富集。关键枢纽转录本包括RABL2B（ENST00000395590）、DNAH1（ENST00000420323）、EFHC1（ENST00000635996）和VWA3A（ENST00000563389），以及转录因子FOXJ1和ZNF474等潜在调控因子。我们的研究结果强调了转录本水平分析在揭示癌前支气管病变生物学新机制方面的重要价值，包括识别与早期肺癌发生相关的潜在生物标志物。
Transcript-Level Biomarkers of Early Lung Carcinogenesis in Bronchial Lesions
肿瘤(癌症)患者之家