Whole Genome DNA Methylation and Gene Expression Profiling of Oropharyngeal Cancer Patients in North-Eastern India: Identification of Epigenetically Altered Gene Expression Reveals Potential Biomarkers

Abstract

Oropharyngeal cancer is a subtype of head and neck squamous cell carcinoma that is associated with unique risk exposures like consumption of smokeless tobacco and areca nut and is highly prevalent in the northeastern region of India, especially Meghalaya. However, the underlying epigenetic and transcriptomic changes in this cancer type is yet to be delineated. We have undertaken a study on genome wide somatic alterations in the DNA methylation and transcriptome in oropharyngeal cancer patients from this region using genome wide techniques in paired tumors and adjacent normal tissues. By using integrative approaches, we have identified 194 epigenetically silenced and 241 epigenetically overexpressed genes in the tumor tissue of these patients. Pathways that are significantly enriched by these genes include the pathways of immune systems, such as the interleukin signaling pathways and Toll-like receptor signaling pathway. Also, osteoclast differentiation pathway was found to be epigenetically upregulated. The pathways enriched by the epigenetically downregulated genes were found to be predominantly those involved in xenobiotic metabolism and keratinization. Two major transcription factors – SPI1 and RUNX1 were identified as epigenetically dysregulated, which further modulates 129 downstream genes. Comparison of our observations with the head and neck cancer data from TCGA revealed distinct DNA methylation and gene expression landscapes which might be specific for oropharyngeal cancer. HPV DNA sequences were not detected in any of the tumor samples in RNA-Seq data. The results obtained in this study might provide improved understanding of the disease.

Single-cell allelic transcriptomic analysis unravels intratumoral gene expression heterogeneity linked to TNBC pathogenesis

“…This hints about a plausible link between random monoallelic expression pattern and DNA methylation in TNBC. Indeed, differential DNA methylation patterns leading to aberrant gene expression levels have been reported for many cancers (Esteller et al 2001; Lakshminarasimhan and Liang 2016; Marthong et al 2020; Batra et al 2021). Importantly, allele-specific DNA methylation has been found to be linked to certain cancers (Vohra et al 2021; Qiangwei Zhou et al 2022).…”

Role of DNA methylation‐based mitotic ageing indices in oral cancer development and recurrence

“…The dataset consisted of 17 pairs of oropharyngeal tumours and adjacent normal tissues and an additional 10 tumour tissues, as described previously (Marthong et al., 2020). Genome‐wide DNA methylation profiling for the dataset was performed using Infinium Methylation (450 K) BeadChips (Illumina).…”

“…Half of the samples were HPV-positive. Genome-wide DNA methylation profiling for the GSE87053 dataset was performed using Infinium Methylation (450 K) BeadChips (Illumina) as described by Basu et al, 2017. The GSE136704 dataset consisted of 17 pairs of oropharyngeal tumours and adjacent normal tissues and an additional 10 tumour tissues, as described previously (Marthong et al, 2020). Genomewide DNA methylation profiling for the GSE136704 dataset was performed using Infinium Methylation (450 K) BeadChips (Illumina).…”

Role of NGS in Oral Squamous Cell Carcinoma

“…The incorporation of nucleotides results in the release of a proton, resulting in a detectable pH shift. This process is continued with each nucleotide cycle, resulting in the formation of a DNA sequence [20]. Ion semiconductor sequencing is quicker and less costly than other NGS technologies, however it has a shorter read length and a greater error rate.…”