Human Colorectal Cancer Stage-dependent Global DNA Hypomethylation of Cancer-associated Fibroblasts

Eduard Ling; Amit Ringel; Ina Sigal-Batikoff; Naim Abu-Freha; Hananya Vaknine; Wledy Friah; Avraham Reshef; Ilia Pinsk; Alexander Fich; Sergio Lamprecht

doi:10.21873/anticanres.10996

Human Colorectal Cancer Stage-dependent Global DNA Hypomethylation of Cancer-associated Fibroblasts

Anticancer Res. 2016 Sep;36(9):4503-7. doi: 10.21873/anticanres.10996.

Authors

Affiliations

¹ Pediatrics Department B, Saban Pediatric Medical Center for Israel, Soroka University Medical Center, Beer Sheva, Israel Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
² Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
³ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
⁴ Institute of Pathology, Wolfson Medical Center, Holon, Israel.
⁵ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Surgery Department B, Soroka University Medical Center, Beer Sheva, Israel.
⁶ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Unit of Colorectal Surgery, Soroka University Medical Center, Beer Sheva, Israel.
⁷ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel sergiol@bgu.ac.il.

PMID: 27630288
DOI: 10.21873/anticanres.10996

Abstract

Background/aim: Cancer-associated fibroblasts (CAFs) play an important role in tumor development and progression. The prevailing consensus favors the view that a specific epigenetic signature underpins the stable CAF phenotype. The aim of the present study was to assess global DNA methylation in CAFs during the adenoma-carcinoma sequence in non-familial sporadic human colorectal cancer (CRC).

Patients and methods: Immunohistochemical staining of nuclear 5-methylcytosine (5'-meCyt) was performed in matched samples of colonic tumor tissue and normal colonic mucosa excised from six patients with adenomas and four with adenocarcinomas. The staining intensity was expressed semi-quantitatively as the immunohistochemical staining score (ISS).

Results: ISS values of human colonic CAFs and adenomatous samples were 14.00±2.2 and 14.08±1.8, respectively, showing no statistically significant difference. In contrast, a marked trend was found towards global DNA hypomethylation in CAFs from adenocarcinomatous specimens compared to matched normal mucosa: ISS: 9.25±2.44 (range=6-11) vs. 16.17±0.75, respectively, p<0.03.

Conclusion: Final stages of cancer development in CRC are associated with global DNA hypomethylation in stromal CAFs.

Keywords: Methylation; colorectal cancer; fibroblasts.

MeSH terms

Adenocarcinoma / metabolism*
Adenoma / embryology*
Biomarkers, Tumor / metabolism
Biopsy
Cancer-Associated Fibroblasts / metabolism*
Cell Line, Tumor
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / metabolism*
DNA Methylation*
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Neoplasm Staging
Phenotype

Substances

Biomarkers, Tumor