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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 semiquantitatively 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.

Original languageEnglish
Pages (from-to)4503-4507
Number of pages5
JournalAnticancer Research
Issue number9
StatePublished - 1 Sep 2016
Externally publishedYes


  • Colorectal cancer
  • Fibroblasts
  • Methylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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