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Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis.

ABSTRACT: Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. However, the diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. A systematic search was performed to identify eligible articles for analysis. The pooled OR showed that SFRP1, SFRP2, SFRP4 and SFRP5 methylation was significantly higher in CRC and benign mucosal lesions than in normal colonic mucosa. When CRC was compared to benign mucosal lesions, SFRP1 and SFRP2 methylation had a significantly higher OR, but methylated SFRP4 and SFRP5 had a similar OR. Moreover, the pooled sensitivity, specificity and AUC (area under the curve) of methylated SFRP2 in feces of patients with CRC vs. healthy subjects was 0.71, 0.94 and 0.94, respectively. Therefore, methylation of SFRP1 and SFRP2 may be significantly correlated with CRC. However, in a study with small sample size, methylated SFRP4 and SFRP5 were not shown to be closely associated with CRC. Additionally, detection of SFRP2 methylation in feces presents a potential noninvasive biomarker for CRC diagnosis.

SUBMITTER: Yang Q

PROVIDER: S-EPMC5034263 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis.

Yang Qihua Q Huang Tao T Ye Guoliang G Wang Bojun B Zhang Xinjun X

Scientific reports 20160923

Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. However, the diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. A systematic search was performed to identify eligible articles for analysis. The pooled OR showed that SFRP1, SFRP2, SFRP4 and SFRP5 methylation was significantly higher in CRC and benign mucosal lesions than in normal colonic mucosa. When CRC was compared to benign mucos ...[more]

PMID: 27659069

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Project description:Background:Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods:CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA-miRNA-mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results:Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion:In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.

Project description:BACKGROUND:As biomarkers, DNA methylation is used to detect colorectal cancer (CRC) and make assessment of CRC prognosis. The published findings showed the association between the methylation of SFRP1, SFRP2, and WIF1, located in the Wnt signaling pathway, and the prognosis of CRC were not consistent. Our study aimed to explore the potential possibility of SFRP1, SFRP2, and WIF1 concomitant promoter methylation as prognostic biomarkers of postoperative CRC patients. METHODS:As a total of 307 sporadic postoperative CRC patients were followed up, we detected SFRP1, SFRP2, and WIF1 methylation obtained from tumor tissues and adjacent non-tumor tissues respectively on the basis of methylation-sensitive high resolution melting analysis. Univariate and multivariate Cox regressions were carried out so as to assess the potential possibility of SFRP1, SFRP2, and WIF1 promoter methylation as predictors of prognosis. Confounders in our study were controlled by Propensity Score (PS) analysis. RESULTS:The SFRP1, SFRP2, and WIF1 methylation levels in tumor tissues were significantly higher than that in adjacent non-tumor tissues (P?<?0.001). SFRP2 hypermethylation was significantly associated with a favorable clinical outcome at the hazard ratio (HR) of 0.343 [95% confidence intervals (CI): 0.164-0.718, P?=?0.005] and 0.410 (95% CI: 0.200-0.842, P?=?0.015) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1 and SFRP2 was significantly associated with a favorable clinical outcome at the HR of 0.333 (95% CI: 0.159-0.694, P?=?0.003) and 0.398 (95% CI: 0.192-0.821, P?=?0.013) in multivariate Cox regression and PS analysis, respectively. Co-hypermethylation of SFRP1, SFRP2 and WIF1 was significantly associated with a favorable clinical outcome at the HR of 0.326 (95% CI: 0.117-0.908, P?=?0.032) and 0.401 (95% CI: 0.146-1.106, P?=?0.077) in multivariate Cox regression and PS analysis, respectively. CONCLUSIONS:SFRP1, SFRP2, and WIF1 were frequently hypermethylated in CRC tumor tissues. It was apparent that the promoter hypermethylation of SFRP2 and co-hypermethylation of SFRP1 and SFRP2 might be considered as independent prognostic predictors for survival advantage of postoperative CRC patients.

Dataset Information

Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis.

Publications

Methylation of SFRP2 gene as a promising noninvasive biomarker using feces in colorectal cancer diagnosis: a systematic meta-analysis.

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