The importance of stool DNA methylation in colorectal cancer diagnosis: A meta-analysis

<div><p>A large number of tumor-related methylated genes have been suggested to be of diagnostic and prognostic values for CRC when analyzed in patients' stool samples; however, reported sensitivities and specificities have been inconsistent and widely varied. This meta-analysis was conducted to assess the detection accuracy of stool DNA methylation assay in CRC, early stages of CRC (advanced adenoma, non-advanced adenomas) and hyperplastic polyps, separately. We searched MEDLINE, Web of Science, Scopus and Google Scholar databases until May 1, 2016. From 469 publications obtained in the initial literature search, 38 studies were included in the final analysis involving 4867 individuals. The true positive, false positive, true negative and false negative of a stool-based DNA methylation biomarker using all single-gene tests considering a certain gene; regardless of a specific gene were pooled and studied in different categories. The sensitivity of different genes in detecting different stages of CRC ranged from 0% to 100% and the specificities ranged from 73% to 100%. Our results elucidated that <i>SFRP1</i> and <i>SFRP2</i> methylation possessed promising accuracy for detection of not only CRC (DOR: 31.67; 95%CI, 12.31–81.49 and DOR: 35.36; 95%CI, 18.71–66.84, respectively) but also the early stages of cancer, adenoma (DOR: 19.72; 95%CI, 6.68–58.25 and DOR: 13.20; 95%CI, 6.01–28.00, respectively). Besides, <i>NDRG4</i> could be also considered as a significant diagnostic marker gene in CRC (DOR: 24.37; 95%CI, 10.11–58.73) and <i>VIM</i> in adenoma (DOR: 15.21; 95%CI, 2.72–85.10). In conclusion, stool DNA hypermethylation assay based on the candidate genes <i>SFRP1</i>, <i>SFRP2</i>, <i>NDRG4</i> and <i>VIM</i> could offer potential diagnostic value for CRC based on the findings of this meta-analysis.</p></div

Performance of a certain gene in all single-gene stool-based DNA methylation biomarker tests included in this meta- analysis.

<p>Performance of a certain gene in all single-gene stool-based DNA methylation biomarker tests included in this meta- analysis.</p

Summary of basic characteristics and performance of studies included in meta-analysis.

<p>Summary of basic characteristics and performance of studies included in meta-analysis.</p

Publication bias of studies in different categories.

<p>CRC: colorectal cancer, TA: total adenoma, TP: total patients.</p

Summary estimates of SFRP1 and SFRP2.

<p>(A) Summary estimates of SFRP1. hypermethylation in stool samples used for TP (CRC+ Adenoma) diagnosis. Red circles represent each study that was included in the meta-analysis. The size of each study is indicated by the size of the red circle. Error bars indicate the 95% confidence interval (CI). Positive LR: positive likelihood ratio, Negative LR: negative likelihood ratio, Diagnostic OR: diagnosis odd ratio, SROC curves: summary receiver operating characteristic curve. (B) Summary estimates of SFRP2. hypermethylation in stool samples used for TP (CRC+ Adenoma) diagnosis. Red circles represent each study that was included in the meta-analysis. The size of each study is indicated by the size of the red circle. Error bars indicate the 95% confidence interval (CI). Positive LR: positive likelihood ratio, Negative LR: negative likelihood ratio, Diagnostic OR: diagnosis odd ratio, SROC curves: summary receiver operating characteristic.</p

Flow diagram of study selection.

<p>Flow diagram of study selection.</p

Atrial Fibrillation and Colonic Neoplasia in African Americans

<div><p>Background</p><p>Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American.</p><p>Methods</p><p>We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression.</p><p>Results</p><p>The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9–2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7–1.6, P = 0.7) were not significantly associated AF compared to control group.</p><p>Conclusions</p><p>AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.</p></div

CAN genes, their functions andcorresponding Accession number.

<p>CAN genes, their functions andcorresponding Accession number.</p

Graphical presentation of methylation frequencies (%) of the CAN genes in the studied populations.

<p>Graphical presentation of methylation frequencies (%) of the CAN genes in the studied populations.</p

Methylation (%) comparison between two populations.

<p>Methylation (%) comparison between two populations.</p