p33ING1b methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions

Abstract

The present study aimed to investigate the feasibility of detecting p33 inhibitor of growth 1b (p33ING1b) gene methylation in fecal DNA as a screening method for colorectal carcinoma (CRC) and precancerous lesions. The methylation of p33ING1b was analyzed in fecal samples from 61 patients with CRCs, 27 patients with precancerous lesions (advanced adenoma) and 20 normal individuals by nested methylation-specific polymerase chain reaction (nMSP) and fecal occult blood test. Methylated p33ING1b was detected in 73.77% of CRC patients and 62.96% of adenoma patients. By contrast, only 5% of normal individuals had methylated p33ING1b. These results indicated 73.77% sensitivity for detecting CRC, 62.96% sensitivity for detecting precancerous lesions and 95% specificity of the assay for detecting CRCs and precancerous lesions. The detection of p33ING1b methylation status by incubation of DNA contained in agarose beads for bisulfite modification, followed by nMSP, is a promising non-invasive screening method for CRCs and precancerous lesions.

Noninvasive DNA methylation biomarkers in colorectal cancer: A systematic review

“…The references of the remaining 72 articles were checked manually, and two articles were further included. Finally, a total of 74 studies were eligible for this systematic review. The flowchart of study selection is shown in Figure .…”

“…Among all the 74 studies, 40 was conducted in the Western countries (including one also performed in West Asia, and one also in East Asia), 30 in East Asia, two in Iran, one in Singapore, and the remaining one unreported.…”

“…In 35 studies, samples were handled and analyzed in a blinded fashion . Methylation‐specific PCR (MSP), quantitative (qMSP) or nested MSP (nMSP) were applied in most studies, quantitative allele‐specific real‐time target and signal amplification (QuARTS) in 3 studies, Methylight or Methyl‐BEAMing (beads, emulsion, amplification and magnetics) in 9 studies, commercial methylation assay kit in 3 studies, pyrosequencing in 2 studies, Melting curve analysis in 2 studies, and methylation microarray in one study.…”

“…In 13 studies, noninvasive samples were collected either within two weeks before or after colonoscopy for histopathology or from newly diagnosed CRC; therefore, question 4 was marked with “yes”. In those 35 blinded studies, DNA methylation status was assessed without histopathological results, and question 10 was labeled as “yes”. The histopathological diagnosis was not avaliable yet at the time of sample collection in two studies, and whether the pathologists were blinded to the methylation results was unclear; therefore, question 11 was labeled as “unclear” for these two studies.…”

“…Notably, numerous hypermethylated genes have been detected in only the feces instead of in blood samples . Progesterone receptor ( PGR ), a member of the steroid receptor superfamily, was the first reported stool‐specific methylation marker in CRC .…”