Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India

Basu, Baidehi and Chakraborty, Joyeeta and Chandra, Aditi and Katarkar, Atul and Baldevbhai, Jadav Ritesh Kumar and Dhar Chowdhury, Debjit and Roy, Jay GopaL and Chaudhuri, Keya and Chatterjee, Raghunath (2017) Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India. Clinical Epigenetics, 9 (13). 01p. -15p..

[img]

PDF
Restricted to IICB Scientists only

Download (2537Kb) | Request a copy

    Abstract

    Background: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples. Results: Genome-wide DNA methylation analysis identified several novel differentially methylated regions associated with OSCC. Hypermethylation is primarily enriched in the CpG-rich regions, while hypomethylation is mainly in the open sea. Distinct epigenetic drifts for hypo- and hypermethylation across CpG islands suggested independent mechanisms of hypo- and hypermethylation in OSCC development. Aberrant DNA methylation in the promoter regions are concomitant with gene expression. Hypomethylation of immune genes reflect the lymphocyte infiltration into the tumor microenvironment. Comparison of methylome data with 312 TCGA HNSCC samples identified a unique set of hypomethylated promoters among the OSCC patients in India. Pathway analysis of unique hypomethylated promoters indicated that the OSCC patients in India induce an anti-tumor T cell response, with mobilization of T lymphocytes in the neoplastic environment. Survival analysis of these epigenetically regulated immune genes suggested their prominent role in OSCC progression. Conclusions: Our study identified a unique set of hypomethylated regions, enriched in the promoters of immune response genes, and indicated the presence of a strong immune component in the tumor microenvironment. These methylation changes may serve as potential molecular markers to define risk and to monitor the prognosis of OSCC patients in India.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/2607
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 16 Mar 2017 16:11
    Last Modified: 21 Mar 2017 16:50
    Official URL: http://dx.doi.org/10.1186/s13148-017-0314-x
    Links:

    Actions (login required)

    View Item