ISSN: 1859 - 2872
CDKN2A alterations and their association with gene expression in non-small cell lung cancer
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Abstract
CDKN2A is an important tumor suppressor gene involved in cell cycle regulation and is frequently altered in non-small cell lung cancer (NSCLC) through multiple mechanisms, including promoter methylation, gene mutation, and copy number variation (CNV). Integrated analyses were performed using DNA methylation, mRNA expression, mutation, CNV, and clinical data from 831 NSCLC patients, including 459 lung adenocarcinoma (LUAD) and 372 lung squamous cell carcinoma (LUSC) cases. The results demonstrated that deep deletion was the molecular alteration most strongly associated with reduced CDKN2A expression, with median expression levels decreasing from 9.86 to 4.91, and the reduction was more pronounced in LUSC than in LUAD. In contrast, CDKN2A mutations were not associated with a corresponding decrease in mRNA expression. These findings indicate that CDKN2A expression in NSCLC is influenced by multiple molecular alterations, among which deep deletion is the alteration most strongly associated with reduced gene expression. In addition, CDKN2A alterations were more prominent in LUSC, suggesting distinct molecular mechanisms between the major histological subtypes of NSCLC.
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References
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