Aberrant promoter methylation of CTHRC1 gene and its clinicopathological characteristics in head and neck cancer

Abstract

Head and neck squamous cell carcinoma (HNSCC) is genetically complex and difficult to treat. Detection in the early stage is challenging, leading to diagnosis at advanced stages with limited treatment options. This study examined the collagen triple helix repeat containing 1 gene (CTHRC1) as a potential biomarker and therapeutic target in HNSCC. Despite documented CTHRC1 upregulation in various cancers, the underlying causes remain unclear. The objective was to investigate potential epigenetic regulation of CTHRC1 expression through the analysis of promoter methylation. CTHRC1 DNA methylation, mRNA, and its protein expression were analysed using The Cancer Genome Atlas (TCGA) HNSCC cohort and oral squamous cell carcinoma (OSCC) patient samples. Functional analysis included scrutinizing the protein–protein interaction network and associations with DisGeNET (disease gene network). Various statistical methods were employed for analysis. HNSCC tumours exhibited significant hypomethylation of CTHRC1 DNA, correlating with advanced disease features. Elevated mRNA and protein expression of CTHRC1 further support its role in disease progression. High CTHRC1 gene expression was associated with a poorer prognosis. The protein interaction network implicated crucial pathways in cancer development and links to oral submucous fibrosis. Despite the limitations of this study, including the use of retrospective data and need for functional experiments, CTHRC1 shows potential as a prognostic predictor and target for therapeutic applications in HNSCC, paving the way for further research and improved patient management.