Methylation pattern of SFRP1 promoter in stool sample is a potential marker for early detection of colorectal cancer

Salehi, Roya; Mohammadi, Mohsen; Emami, Mohammad Hasan; Salehi, Ahmad

doi:10.4103/2277-9175.105169

Cited by 24 publications

(22 citation statements)

References 36 publications

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“…The frequency of SFRP1 gene promoter methylation in our patients was 72.2%. Previous studies, have shown a frequency ranging from 52-95% in colorectal cancer (Rawson et al, 2011;Barták, 2017;Zhou et al, 2015;Meng et al, 2011;Dallol et al, 2012;Salehi et al, 2012). In present study we noted a slightly higher incidence of hypermethylation of SFRP1 in male patients than females (75.8% vs. 66.7%), however this difference was not statistically significant (p=0.54).…”

Section: Discussioncontrasting

confidence: 67%

Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

Kumar

Gosipatala

Pandey

et al. 2019

Asian Pac J Cancer Prev

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Background:The development of colorectal carcinoma (CRC) involves many genetic and epigenetic alterations and methylation being an important epigenetic event has been described as a diagnostic and prognostic biomarker. Secreted Frizzled- Related Protein 1 (SFRP1) gene regulates diverse physiological processes via the Wnt signaling. Promoter hypermethylation of SFRP1 gene is an epigenetic regulation mechanism that downregulates SFRP1 protein level in the tumor, and happens to be one of the significant events in colorectal carcinogenesis. We studied the clinicopathological relationship of CRC including survival outcomes with SFRP1 gene promoter methylation.Methods:We evaluated promoter methylation status of SFRP1 gene by methylation-specific PCR (MS-PCR) in the tumor tissue in 54 cases of stage II-III CRC patients in north India. The MS-PCR result was further validated by bisulfite sequencing.Results:SFRP1 gene was methylated in 72.2% cases and un-methylated in 27.8%. We found, that SFRP1 gene methylation in tumor was associated with lymph node invasion (p=0.05). The mean overall survival was 22.318 months and 45.173 months respectively for patients with methylated and unmethylated SFRP1 gene (p= 0.010, log rank test), (HR = 17.313, 95% CI: 2.021-148.290 P=0.009).Conclusion:Study indicates that promoter methylation of SFRP1 gene is associated with lymph-node metastasis and poor mean overall survival and it can be a prognostic marker in CRC.

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Section: Discussioncontrasting

confidence: 67%

Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

Kumar

Gosipatala

Pandey

et al. 2019

Asian Pac J Cancer Prev

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“…Wnt signaling pathway acts as an oncogenic way that aberrant activation of the Wnt pathway may give rise to the variety of human cancers, especially in CRC. SFRP2 gene, an important member of the SFRP family, functions as a negative regulator of the oncogenic Wnt pathway through competing with frizzled membrane-bound receptors that can use it as an appropriate marker in CRCs screening 9. Mόller et al 24.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, FOBT screening decreases only CRC mortality but not the incidence of CRC, and it is not able to detect precursor lesions 78. Colonoscopy is an invasive method that causes adverse effects including postpolypectomy bleeding and perforation;8 for this reason, the primary goal is to identify useful screening tools such that it could increase the sensitivity and specificity of screening without invasive actions 89. Molecular and genetic study can play a key role in the detection of CRC because genetic alterations are the main causes of colorectal neoplasia 10.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly enough, the number of genes silenced by epigenetic mechanisms is more than the number of genetic mutations in CRC that it put forward an important role of epigenetic alterations 15. There are a great number of genes that will be used as DNA methylation biomarkers ahead that would increase the sensitivity of noninvasive screening tests for CRC 916. SFRPs genes have a key role in the inhibitory modulators of a tumorigenic pathway (the Wnt signaling pathway), and hence silencing of the SFRP genes is the leading cause of Wnt pathway activation that gives rise to the genesis of the colorectal tumor 17.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation analysis of secreted frizzled-related protein 2 gene for the early detection of colorectal cancer in fecal DNA

2016

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Background:The early detection of colorectal cancer (CRC) with high sensitivity screening is essential for the reduction of cancer-specific mortality. Abnormally methylated genes that are responsible for the pathogenesis of cancers can be used as biomarkers for the detection of CRC. The methylation status of the secreted frizzled-related protein 2 (SFRP2) gene was evaluated for their use as a marker in the noninvasive detection of CRC.Materials and Methods:Methylation-specific polymerase chain reaction was performed to analyze the promoter CpG methylation of SFRP2 in the fecal DNA of 25 patients with CRC and 25 individuals exhibiting normal colonoscopy results.Results:Promoter methylation levels of SFRP2 in CRC patients and in healthy controls were 60% and 8%, respectively. Methylation of the SFRP2 promoter in fecal DNA is associated with the presence of colorectal tumors.Conclusion:Hence, the detection of aberrantly methylated DNA in fecal samples may present a promising, noninvasive screening method for CRC.

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“…Epigenetic SFRP1 inactivation is linked to the upregulation of Wnt / β-catenin cascade in CRC; Wnt / β-catenin repression has also been considered a mechanism that inhibits tumor cell growth and prevents metastatic invasion ( Figure 1 ) 22 . SFPR2 and SFRP1 methylation in stool also exnibits high sensitivity and specificity for CRC detection 26-40 . SFRP2 methylation for CRC identification in stool samples reaches a sensitivity of 90% and specificity of 77% 31 .…”

Section: Multiple Dna Methylation Biomarkersmentioning

confidence: 96%

DNA methylation assay for colorectal carcinoma

Chen¹,

Wang

Chen

2017

Cancer Biology &Amp; Medicine

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Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involvesAPC/β-catenin characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions inDNA mismatch repair genes. Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis. Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction (qPCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool qPCR methylation test may also be an enhanced tool for CRC and adenoma screening.

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Methylation pattern of SFRP1 promoter in stool sample is a potential marker for early detection of colorectal cancer

Cited by 24 publications

References 36 publications

Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

DNA methylation analysis of secreted frizzled-related protein 2 gene for the early detection of colorectal cancer in fecal DNA

DNA methylation assay for colorectal carcinoma

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