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Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

Ganapathi, SK; Beggs, AD; Hodgson, SV; Kumar, D (2014) Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance. British Journal of Cancer, 111 (8). pp. 1581-1589. ISSN 1532-1827 https://doi.org/10.1038/bjc.2014.477
SGUL Authors: Hodgson, Shirley Victoria Ganapathi, Senthil Kumar Kumar, Devinder

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Abstract

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies.

Item Type: Article
Additional Information: © 2014 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Keywords: Adenocarcinoma, Base Sequence, Colorectal Neoplasms, DNA Methylation, DNA Primers, Female, Forkhead Transcription Factors, Gene Expression, Humans, Interferon-gamma, Male, Microsatellite Instability, Prognosis, Reverse Transcriptase Polymerase Chain Reaction, Survival Analysis, Tumor Necrosis Factor-alpha, expression, IFNG, TNF, FOXP3, survival, Oncology & Carcinogenesis, 1112 Oncology And Carcinogenesis
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: British Journal of Cancer
ISSN: 1532-1827
Language: eng
Dates:
DateEvent
14 October 2014Published
PubMed ID: 25225903
Web of Science ID: WOS:000343932600014
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107300
Publisher's version: https://doi.org/10.1038/bjc.2014.477

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