DNA Methylation Events in Transcription Factors and Gene Expression Changes in Colon Cancer

Abstract

Aim: Gain insight about the role of DNA methylation in the malignant growth of colon cancer. Patients & methods: Methylation and gene expression from 90 adjacent-tumor paired tissues and 48 healthy tissues were analyzed. Tumor genes whose change in expression was explained by changes in methylation were identified using linear models adjusted for tumor stromal content. Results: No differences in methylation were found between adjacent and healthy tissues, but clear differences were found between adjacent and tumor samples. We identified hypermethylated CpG islands located in promoter regions that drive differential gene expression of transcription factors and their target genes. Conclusion: Changes in methylation of a few genes provoke important changes in gene expression, by expanding the signal through transcription activation/repression.

Keywords::

• colon cancer
• differential methylation
• DNA methylation
• gene expression
• transcription factors

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2020-0029

Acknowledgments

The authors would like to thank G Aiza for her technical assistance with DNA extractions, T Berenguer for his statistical advice and C Atencia, P Medina and I Padrol for their contribution with the clinical annotation of the samples

Financial & competing interests disclosure

This work was supported by the Catalan Institute of Oncology, the Instituto de Salud Carlos III and the Spanish Ministry of Science, Innovation and Universities, co-funded by FEDER funds – a way to build Europe – (grants PI08-1635, PS09-1037, PI11-1439, RTI2018-094009-B-I00), CIBERESP (grant CB07/02/2005), the Catalan Government DURSI (grant 2017SGR723) and the Spanish Association Against Cancer (AECC) Scientific Foundation. This work was supported by COST Action CA17118 TransColonCan. R Carreras-Torres is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 796216. The authors thank ICObiobanc, Biobank HUB-ICO-IDIBELL PT17/0015/0024 and CERCA Program, Generalitat de Catalunya for institutional support. V Moreno is consultant to Bioiberica S.A.U. and Grupo Ferrer S.A., received research funds from Universal DX and is co-investigator in grants with Aniling S.L. M A Peinado is cofounder and equity holder of Aniling S.L. M A Peinado lab has received research funding from Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The Clinical Research Ethics Committee of the Bellvitge Hospital approved the study protocol (number PR178/11), and all individuals provided written informed consent to participate and for genetic analyses to be done on their samples. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Data generated used in this work is available in the project website www.colonomics.org and in the Gene Expression Omnibus (GEO) database in project PRJNA188510, with accession number GSE44076 (gene expression) and GSE131013 (DNA methylation).

Additional information

Funding

This work was supported by the Catalan Institute of Oncology, the Instituto de Salud Carlos III and the Spanish Ministry of Science, Innovation and Universities, co-funded by FEDER funds – a way to build Europe – (grants PI08-1635, PS09-1037, PI11-1439, RTI2018-094009-B-I00), CIBERESP (grant CB07/02/2005), the Catalan Government DURSI (grant 2017SGR723) and the Spanish Association Against Cancer (AECC) Scientific Foundation. This work was supported by COST Action CA17118 TransColonCan. R Carreras-Torres is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 796216. The authors thank ICObiobanc, Biobank HUB-ICO-IDIBELL PT17/0015/0024 and CERCA Program, Generalitat de Catalunya for institutional support. V Moreno is consultant to Bioiberica S.A.U. and Grupo Ferrer S.A., received research funds from Universal DX and is co-investigator in grants with Aniling S.L. M A Peinado is cofounder and equity holder of Aniling S.L. M A Peinado lab has received research funding from Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.