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- Title
Transcript-Level Biomarkers of Early Lung Carcinogenesis in Bronchial Lesions.
- Authors
Pyatnitskiy, Mikhail A.; Poverennaya, Ekaterina V.
- Abstract
Simple Summary: Premalignant lesions in the bronchial epithelium mark the early stages of squamous cell lung carcinoma and are difficult to detect using traditional methods. Therefore, there is a critical need to identify biomarkers that can aid in their detection and characterization. Here, we perform system-biology analysis of transcriptomic profiles of premalignant lesions with the aim of deriving novel biomarkers of bronchial lesions at the transcript level instead of the traditional gene-level approach. We found transcripts that are specifically associated with premalignant lesions along with several transcription factors that are likely potential regulators of the corresponding genes. The identified transcripts and transcription factors may serve as potential biomarkers or drug targets for prevention of squamous cell lung carcinoma. Furthermore, deeper understanding of the underlying biology may lead to the development of novel diagnostic tools and therapeutic strategies, impacting the broader research community engaged in lung cancer studies. 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.
- Subjects
MITOCHONDRIAL physiology; BRONCHIAL diseases; PHOSPHORYLATION; RESEARCH funding; PRECANCEROUS conditions; EARLY detection of cancer; TUMOR markers; CELLULAR signal transduction; OXIDATIVE stress; RNA; LUNG tumors; GENE expression profiling; CARCINOGENESIS
- Publication
Cancers, 2024, Vol 16, Issue 12, p2260
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16122260