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Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease

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Tumor Biology

Abstract

Promoter methylation in various tumor suppressor genes is reported to influence gallbladder carcinogenesis. Here, we aimed to identify methylation status in gallbladder cancer (GBC) by performing a comprehensive genome-wide DNA methylation profiling. The methylation status of 485,577 CpG sites were investigated using Illumina’s Infinium Human Methylation 450 BeadChip array in 24 tissues (eight each of tumor, adjacent non-tumor, and gallstone). About 33,443 differentially methylated sites (DMRs) were obtained in the whole human genome, of which 24,188 (72 %) were hypermethylated and 9255 (28 %) were hypomethylated. The data also revealed that majority of the DMRs are localized on the proximal promoter region [Transcription start sites (TSS200, TSS1500) and 5′ untranslated region (5′UTR)] and first exon. Exclusion of first exon detected a total of 10,123 (79 %) hypermethylated and 2703 (21 %) hypomethylated sites. Comparative analysis of the later with our differential proteomics data resulted in identification of 7 hypermethylated or down-regulated (e.g., FBN1, LPP, and SOD3) and 61 hypomethylated or up-regulated markers (e.g., HBE1, SNRPF, TPD52) for GBC. These genes could be further validated on the basis of their methylation/expression status in order to identify their utility to be used as biomarker/s for early diagnosis and management of GBC.

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Acknowledgments

This study was supported by the Department of Science and Technology, Government of India, New Delhi, India (DST No. SR/SO/HS/0161/2010). We are thankful to laboratory members, Sonam Shrivastava and Anshu Agarwal for their assistance in mining the gene details. The authors are also thankful to the patients and their family members for their active cooperation in this study.

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  1. Mustafa Ahmed Barbhuiya

    Present address: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, MD, Baltimore, USA

Authors and Affiliations

  1. Molecular and Human Genetics Division, Centre for Genomics, Jiwaji University, Gwalior, Madhya Pradesh, 474011, India

    Preeti Sharma, Shushruta Bhunia, Satish S. Poojary, Dinesh S. Tekcham, Mustafa Ahmed Barbhuiya & Pramod Kumar Tiwari

  2. Cancer Hospital and Research Institute, Cancer Hills, Gwalior, Madhya Pradesh, 474009, India

    Sanjiv Gupta & Braj Raj Shrivastav

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  1. Preeti Sharma
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Correspondence to Pramod Kumar Tiwari.

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Preeti Sharma, Shushruta Bhunia, and Satish S. Poojary contributed equally to this work.

Electronic supplementary material

Supplementary file 1

List of common genes in all data sets (XLSX 41 kb)

Supplementary file 2

List of genes based on pathway Ontology (XLSX 10 kb)

Supplementary file 3

(DOCX 11 kb)

Supplementary file 4

(DOCX 14 kb)

Supplementary file 5

List of unique 903 genes found only in tumor-with-stone samples (XLSX 78 kb)

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Sharma, P., Bhunia, S., Poojary, S.S. et al. Global methylation profiling to identify epigenetic signature of gallbladder cancer and gallstone disease. Tumor Biol. 37, 14687–14699 (2016). https://doi.org/10.1007/s13277-016-5355-9

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