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



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.



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.
Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India.
Baidehi
B
Basu
Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India.
Joyeeta
J
Chakraborty
Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India.
Aditi
A
Chandra
Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India.|Molecular Genetics Division, CSIR-Indian Institute of Chemical biology, 4 Raja S C Mullick Road, Kolkata, 700 032 India.
Atul
A
Katarkar
Dr. R Ahmed Dental College & Hospital, 114, A J C Bose Road, Kolkata, India.
Jadav Ritesh Kumar
JRK
Baldevbhai
Dr. R Ahmed Dental College & Hospital, 114, A J C Bose Road, Kolkata, India.
Debjit
D
Dhar Chowdhury
Dr. R Ahmed Dental College & Hospital, 114, A J C Bose Road, Kolkata, India.
Jay Gopal
JG
Ray
Molecular Genetics Division, CSIR-Indian Institute of Chemical biology, 4 Raja S C Mullick Road, Kolkata, 700 032 India.
Keya
K
Chaudhuri
Human Genetics Unit, Indian Statistical Institute, 203 B. T. Road, Kolkata, 700108 India.
Raghunath
R
Chatterjee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation / Q000276:immunology*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000276:immunology; D055106:Genome-Wide Association Study / Q000379:methods; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
Bisulfite cloning and sequencing; CTLA4; CpG island; Differentially methylated regions; Gene expression; Methylation-specific PCR; Oral squamous cell carcinoma