Diagnostic Value of Fecal MicroRNAs for Colorectal Cancer: a Meta-Analysis

Wang, Chengzu; Zhao, Kai; Rong, Qiji

doi:10.7754/clin.lab.2015.150507

Cited by 6 publications

(6 citation statements)

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“…Heterogeneity. Heterogeneity underlying eligible studies was mirrored by the examination of threshold and nonthreshold effects among studies (25,27). As shown in Table II, Spearman's correlation coefficient of the overall effect size revealed a P>0.05, suggesting that no significant heterogeneity generated from the threshold effect.…”

Section: Resultsmentioning

confidence: 98%

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A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Zhang¹,

Zhang³

et al. 2017

Biomedical Reports

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Abstract. The methylation status of septin-9 gene in plasma has been developed as a promising biomarker to aid in the diagnosis of colorectal cancer (CRC). In this study, we aimed to evaluate the overall diagnostic ability of septin-9 methylation for detection of CRC. Studies on the diagnostic performance of plasma septin-9 in CRC were searched from the online databases up to January 31st, 2017. Risk of bias among the studies was estimated according to the Quality Assessment of Studies of Diagnostic Accuracy included in the Systematic Reviews (QUADAS) II checklist. The aggregation of the effect sizes was enabled by utilizing a bivariate analysis model. A meta-regression test and influence analysis were conducted to determine the underlying sources of heterogeneity. According to the predefined criteria, 1,462 patients with CRC from 14 eligible trials were included. The quantitative meta-analyses showed that methylated septin-9 in plasma sustained a pooled sensitivity of 0.67 (95% CI, 0.61-0.73) and specificity of 0.89 (95% CI, 0.86-0.92) in discriminating CRC patients from cancer-free individuals, along with an area under the curve of 0.87. Moreover, the stratified analyses grouped by ethnicity demonstrated that methylayted septin-9 testing achieved a better sensitivity of 0.72 (95% CI, 0.68-0.76) in the European-based population group and a higher specificity of 0.90 (95% CI, 0.88-0.92) in the Asian-based population group. Plasmic methylated septin-9 suggests a promising diagnostic efficacy in confirming CRC. However, more studies are required to confirm our findings.

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Section: Resultsmentioning

confidence: 98%

“…Heterogeneity can be interpreted by both threshold and non-threshold effects (25,27). The threshold effect can be caused by different cut-off value settings as well as objective methods.…”

Section: Discussionmentioning

confidence: 99%

A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Zhang¹,

Zhang³

et al. 2017

Biomedical Reports

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“…More recently, fecal content has emerged as new and interesting source of miRNA biomarkers for IBD and colorectal cancer 12. For example, fecal miRNAs were proposed as potential biomarkers for colorectal cancer 13, 30, and a recent study showed that miRNAs in feces correlate with disease activity in IBD patients, and thus warrant further study as potential biomarkers for this disease 31. A limitation of our analysis is that, due to material limitations, microbiota and miRNA profiles were not analyzed at the same time point in our recipient mice.…”

Section: Discussionmentioning

confidence: 99%

Host-derived fecal microRNAs can indicate gut microbiota healthiness and ability to induce inflammation

Viennois¹,

Chassaing²,

Tahsin³

et al. 2019

Theranostics

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Disruption of intestine-microbiota symbiosis can result in chronic gut inflammation. We hypothesize that assessing the initial inflammatory potential of the microbiota in patients is essential and that host-derived miRNAs, which can be found in feces, could fulfill this function. We investigated whether the gut microbiota composition impacts the fecal miRNA profile and thereby indicates its ability to influence intestinal inflammation. Methods : We used high-throughput qPCR to compare fecal miRNA profile between germ-free and conventional mice. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas (IL10 -/- and TLR5 -/- associated microbiota) was performed. Results : We identified 12 fecal miRNAs impacted by the presence of a microbiota. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas associated with the development of intestinal inflammation (IL10 -/- and TLR5 -/- associated microbiota) yielded distinctively altered fecal miRNA profiles compared to that of mice receiving a “healthy” microbiota. Correlation analysis revealed the existence of interactions between the 12 abovementioned miRNAs and specific microbiota members. Conclusion : These results showed that fecal miRNA profile can be differentially and specifically impacted by microbiota composition, and that miRNA could importantly serve as markers of the colitogenic potential of the microbiota. This is particularly relevant to assess individual state of the microbiota in patients with dysbiosis-related disorders, such as IBD and potentially determine their ability to respond to therapeutics.

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“…13,14 Evaluating the downstream molecular symptoms derived from precancerous variants could improve sensitivity for adenomas. [15][16][17] However, analysis of human RNA biomarkers in stool samples is extremely challenging due to extensive RNA degradation and a high bacterial transcript burden. 18,19 Previous studies report that 25%-50% of stool samples evaluated for eukaryotic RNA are inadequate for downstream analysis.…”

Section: Introductionmentioning

confidence: 99%

Stool-derived eukaryotic RNA biomarkers for detection of high-risk adenomas

Barnell

Kang

Barnell³

et al. 2019

Preprint

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Abbreviations AUC area under the curve ANOVA analysis of variance CRC colorectal cancer DE differentially expressed FC fold-change FIT fecal immunochemical test HRA high-risk adenoma LRA low-risk adenoma MRA medium-risk adenoma NPV negative predictive value PPV positive predictive value ROC receiver operating characteristic seRNA stool-derived eukaryotic RNA AbstractBackground and aims: Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. Mortality is largely attributable to low patient compliance with screening and a subsequent high frequency of late-stage diagnoses. Noninvasive methods, such as stool-or blood-based diagnostics could improve patient compliance, however, existing techniques cannot adequately detect high-risk adenomas (HRAs) and early-stage CRC. Methods: Here we apply cancer profiling using amplicon sequencing of stool-derived eukaryotic RNA for 275 patients undergoing prospective CRC screening. A training set of 154 samples was used to build a random forest model that included 4 feature types (differentially expressed amplicons, total RNA expression, demographic information, and fecal immunochemical test results). An independent hold out test set of 121 patients was used to assess model performance. Results: When applied to the 121-patient hold out test set, the model attained a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 for CRC and a ROC AUC of 0.87 for CRC and HRAs. In aggregate, the model achieved a 91% sensitivity for CRC and a 73% sensitivity for HRAs at an 89% specificity for all other findings (medium-risk adenomas, low-risk adenomas, benign polyps, and no findings on a colonoscopy). Conclusion: Collectively, these results indicate that in addition to early CRC detection, stool-derived biomarkers can accurately and noninvasively identify HRAs, which could be harnessed to prevent CRC development for asymptomatic, average-risk patients.

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Diagnostic Value of Fecal MicroRNAs for Colorectal Cancer: a Meta-Analysis

Cited by 6 publications

References 0 publications

A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

A pooled analysis of the diagnostic efficacy of plasmic methylated septin-9 as a novel biomarker for colorectal cancer

Host-derived fecal microRNAs can indicate gut microbiota healthiness and ability to induce inflammation

Stool-derived eukaryotic RNA biomarkers for detection of high-risk adenomas

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