DNA methylation and expression of the folate transporting genes in colorectal cancer

• This study investigated the DNA methylation pattern and protein expression of the FOLR1, PCFT, and RFC1 genes in colorectal cancer (CRC) tissue. Our results showed statistically significant differences in the DNA methylated fraction of all three genes at several gene regions, we identified 3 differentially methylated CpG sites in the FOLR1 gene, 5 CpG sites in the PCFT gene, and 6 CpG sites in the RFC1 gene. We observed a pronounced expression of the FRα and RFC proteins in both the cancer and normal tissues, though the proteins were moderately expressed in cancer compared to the high expression in the paired healthy mucosa. The PCFT protein was undetectable or expressed very low in both tissues. Higher methylated fractions of the CpG sites 3-5 in the RFC1 gene were associated with a lower protein expression. When analyzing the association between DNA methylation and tumor characteristics (differentiation, location, primary tumor stage and lymph node involvement) we detected lower methylated fraction of specific CpG sites in the RFC1 gene in CRC located in the distal colon and rectum compared to the proximal colon. In the FOLR1 gene, we found CpG sites with a lower methylated fraction of colorectal cancers with the primary tumor stage 4 (pT4) compared to the pT2 and pT3 stages. Our results did not show association between the RFC and FRα protein expression and tumor stage, TNM classification or tumor location. In conclusion, these data suggest that there is a possible epigenetic regulation by DNA methylation of the RFC1 gene in the colorectal cancer.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

Nyckelord

CpG

T-DMR

reduced folate carrier

CRC

immunohistochemistry

Biomedicin

Biomedicine

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)