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Fecal microRNAs, Fecal microRNA Panels, or Combinations of Fecal microRNAs with Fecal Hemoglobin for Early Detection of Colorectal Cancer and Its Precursors: A Systematic Review.

ABSTRACT: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Fecal miRNAs have been suggested to be promising biomarkers for CRC early detection. We aimed to conduct a systematic literature review on the diagnostic performance of fecal miRNA markers for CRC and its precursors. PubMed and Web of Science were searched to retrieve relevant articles published up to 7 December 2021. Information on study design, characteristics of study population, pre-analytics (sample collection, processing, and storage), fecal miRNA extraction and quantification technologies, and diagnostic performance (including sensitivity, specificity, and area under the curve (AUC)) were summarized. Twenty studies reporting on 31 individual miRNAs and 16 miRNA panels (with 2-9 markers) for CRC diagnosis were identified. Substantial heterogeneity existed regarding stool sample collection, processing, storage, and miRNA extraction and normalization. For two individual miRNAs and one miRNA panel, values ≥ 80% were reported for both sensitivity and specificity; however, none of these results were either internally or externally validated. In a study among fecal immunochemical test-positive cases recruited from a true screening setting, better diagnostic performance was identified and internally validated for a combination panel including two miRNAs, fecal hemoglobin level, and patient age and sex, compared with fecal hemoglobin concentration alone. Fecal miRNAs or miRNA panels, possibly in combination with fecal hemoglobin test, may be promising candidates for noninvasive CRC early detection. However, large prospective and well-designed studies in CRC screening cohorts are required to validate promising miRNAs or miRNA panels.

SUBMITTER: Zhao Z

PROVIDER: S-EPMC8750731 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceGiven a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy.ObjectiveTo demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening.Design, setting, and participantsA retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes.Main outcomes and measurementsA spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023.ResultsUsing data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening.Conclusion and relevanceThe gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.

Project description:ObjectivesThis study aimed to identify colorectal cancer (CRC)-associated phylogenetic and functional bacterial features by a large-scale metagenomic sequencing and develop a binomial classifier to accurately distinguish between CRC patients and healthy individuals.MethodsWe conducted shotgun metagenomic analyses of fecal samples from a ZhongShanMed discovery cohort of 121 CRC and 52 controls and SouthernMed validation cohort of 67 CRC and 44 controls. Taxonomic profiling and quantification were performed by direct sequence alignment against genome taxonomy database (GTDB). High-quality reads were also aligned to IGC datasets to obtain functional profiles defined by Kyoto Encyclopedia of Genes and Genomes (KEGG). A least absolute shrinkage and selection operator (LASSO) classifier was constructed to quantify risk scores of probability of disease and to discriminate CRC from normal for discovery, validation, Fudan, GloriousMed, and HongKong cohorts.ResultsA diverse spectrum of bacterial and fungi species were found to be either enriched (368) or reduced (113) in CRC patients (q<0.05). Similarly, metabolic functions associated with biosynthesis and metabolism of amino acids and fatty acids were significantly altered (q<0.05). The LASSO regression analysis of significant changes in the abundance of microbial species in CRC achieved areas under the receiver operating characteristic curve (AUROCs) of 0.94 and 0.91 in the ZhongShanMed and SouthernMed cohorts, respectively. A further analysis of Fudan, GloriousMed, and HK cohorts using the same classification model also demonstrated AUROC of 0.80, 0.78, and 0.91, respectively. Moreover, major CRC-associated bacterial biomarkers identified in this study were found to be coherently enriched or depleted across 10 metagenomic sequencing studies of gut microbiota.ConclusionA coherent signature of CRC-associated bacterial biomarkers modeled on LASSO binomial classifier maybe used accurately for early detection of CRC.

Project description:BackgroundTo what extent the risk for colorectal cancer (CRC) death among noncompliers of colonoscopy is elevated following positive fecal immunological testing and whether the elevated risk varies with the fecal hemoglobin concentration (f-Hb) and location of CRC have not been researched.MethodsWe used data on 59 389 individuals (4.0%) among 1 489 937 Taiwanese screenees age 50 to 69 years with f-Hb 20??g hemoglobin or more per gram of feces from 2004 to 2009. They were classified into 41 995 who received colonoscopy and 10 778 who received no confirmatory examination; the latter was categorized into three risk groups according to f-Hb (20-49, 50-99, and 100+). Mortality from CRC as the primary end point was monitored until December 31, 2012.ResultsA 1.64-fold (95% confidence interval [CI] = 1.32 to 2.04) increased risk for CRC death for the noncolonoscopy group as opposed to the colonoscopy group adjusting for differences in baseline characteristics. A gradient relationship was noted between cumulative mortality and age- and sex-adjusted f-Hb categories with 1.31-fold (95% CI?=?1.04 to 1.71), 2.21-fold (95% CI?=?1.55 to 3.34), and 2.53-fold (95% CI?=?1.95 to 3.43) increased risk, respectively, for the 20-49, 50-99, and 100+ risk groups in the noncolonoscopy group compared with the colonoscopy group. The noncolonoscopy group led to a statistically significant 1.75-fold increased risk (95% CI?=?1.35 to 2.33) for CRC of the distal colon but a statistically nonsignificant 1.11-fold increased risk (95% CI?=?0.70 to 1.75) for the proximal colon, compared with the colonoscopy group. When the comparator was limited to subjects whose colonoscopy was completed to the cecum, the statistically significantly elevated risk for CRC mortality was seen for both distal and proximal colon in the noncolonoscopy group.ConclusionsAfter a positive fecal immunochemical test, colonoscopy can reduce by about half the number of deaths from CRC. Among colonoscopy noncompliers, higher f-Hb is associated with an increased risk of mortality from CRC in a dose-response manner.

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Fecal microRNAs, Fecal microRNA Panels, or Combinations of Fecal microRNAs with Fecal Hemoglobin for Early Detection of Colorectal Cancer and Its Precursors: A Systematic Review.

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