Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer.

BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

[Met-analysis on randomized controlled clinical trials of acupuncture and moxibustion on constipation].

OBJECTIVE: To assess the efficacy of acupuncture and moxibustion on constipation. METHODS: A retrieval on literatures concerning treatment of constipation with acupuncture was carried out in databases of VIP, CNKI, WANFANG and PubMed. And meta-analyses were conducted on randomized controlled trial (RCT) and controlled clinical trial (CCT) which met the enrolling requirements. RESULTS: A total number of 15 papers involving 1 052 patients were concluded. The result indicated that the curative rate of acupuncture and moxibustion on constipation is better than ordinary medication (RR = 1.92, 95% CI 1.61-2.30, Z = 7.18, P < 0.000 01). And statistical significance can be found between acupuncture-moxibustion treatment and the routine medicine treatment (RR = 1.26, 95% CI 1.18-1.34, Z = 7.26, P < 0.000 01). In the comparison of abdominal pain, defecation duration and general symptom scores, statistical significance can be found between the differences of acupuncture and moxibustion group and control group (abdominal pain: WMD = -0.22, 95% CI-0.32-0.12, Z = 4.28, P < 0.000 1; defecation duration: WMD = -0.47, 95% CI-0.79-0.15, Z = 2.85, P < 0.004; general symptom scores: WMD = -0.41, 95% CI-0.79-0.03, Z = 2.13, P = 0.03). CONCLUSION: Acupuncture and moxibustion is effective to treat constipation. It has certain advantage when compare with the routine medication treatment. However, since singleness still exists in the index of assessment on therapeutic effect of constipation, and the number of RCT and CCT literatures, especially high-quality, large samples and multi-center reports were still not enough, further studies are still necessary for approving the above conclusions.