scholarly journals Multitarget Stool mRNA Test for Detecting Colorectal Cancer Lesions Including Advanced Adenomas

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1228
Author(s):  
Elizabeth Herring ◽  
Éric Tremblay ◽  
Nathalie McFadden ◽  
Shigeru Kanaoka ◽  
Jean-François Beaulieu
Keyword(s):  
Colorectal Cancer ◽  
Precancerous Lesions ◽  
Roc Curves ◽  
Screening Methods ◽  
Roc Curve Analysis ◽  
Non Invasive ◽  
Mrna Targets ◽  
Fit Testing ◽  
Stool Samples ◽  
Advanced Adenomas

Current approved non-invasive screening methods for colorectal cancer (CRC) include FIT and DNA-FIT testing, but their efficacy for detecting precancerous lesions that are susceptible to progressing to CRC such as advanced adenomas (AA) remains limited, thus requiring further options to improve the detection of CRC lesions at earlier stages. One of these is host mRNA stool testing. The aims of the present study were to identify specific stool mRNA targets that can predict AA and to investigate their stability under a clinical-like setting. A panel of mRNA targets was tested on stool samples obtained from 102 patients including 78 CRC stage I-III and 24 AA as well as 32 healthy controls. Area under the receiver operating characteristic (ROC) curves were calculated to establish sensitivities and specificities for individual and combined targets. Stability experiments were performed on freshly obtained specimens. Six of the tested targets were found to be specifically increased in the stools of patients with CRC and three in the stools of both AA and CRC patients. After optimization for the choice of the 5 best markers for AA and CRC, ROC curve analysis revealed overall sensitivities of 75% and 89% for AA and CRC, respectively, for a ≥95% specificity, and up to 75% and 95% for AA and CRC, respectively, when combined with the FIT score. Targets were found to be stable in the stools up to 3 days at room temperature. In conclusion, these studies show that the detection of host mRNA in the stools is a valid approach for the screening of colorectal cancerous lesions at all stages and is applicable to a clinical-like setup.

scholarly journals The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ane Sørlie Kværner ◽  
Einar Birkeland ◽  
Cecilie Bucher-Johannessen ◽  
Elina Vinberg ◽  
Jan Inge Nordby ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Gut Microbiome ◽  
Precancerous Lesions ◽  
Colorectal Carcinogenesis ◽  
Screening Tools ◽  
Screening Methods ◽  
Crc Screening ◽  
Link Type ◽  
Incidence And Mortality

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550.

scholarly journals Detection Rate of Colorectal Cancer or Precancer Adenoma by Colonoscopy After 1, 2, or 3 Positive Results via Fecal Immunochemical Testing

2019 ◽  
Vol 50 (3) ◽  
pp. 263-267
Author(s):  
Jill A Hancock ◽  
Glen A Palmer
Keyword(s):  
Colorectal Cancer ◽  
Screening Program ◽  
Optimal Number ◽  
Screening Methods ◽  
Data Set ◽  
Crc Screening ◽  
Fecal Immunochemical Testing ◽  
Fit Testing ◽  
Risk Patients ◽  
Standard Practices

Abstract Background Single-vial fecal immunochemical testing (FIT) is an accepted method of colorectal cancer (CRC) screening. The available 3-vial FIT data set allows for comparison of colonoscopy results using various screening methods. Objective To determine the optimal number of vials for a strong FIT-screening program by examining whether using only a single vial impacts the use of colonoscopy for CRC screening. Methods Patients were given 3-vial FIT collection kits that were processed with a positive hemoglobin cut-off detection level of 100 ng per mL. If FIT results were positive, colonoscopy testing was performed using standard practices. Results Detection of CRC and precursor adenoma was examined in 932 patients, with a positive colonoscopy sensitivity of 56.2% and 3.0% CRC detection after 3-vial FIT; after single-vial screening, those values were 60.9% and 4.7%, respectively. Conclusions Prescreening patients with FIT testing before colonoscopy allows colonoscopy testing to be targeted to higher-risk patients. Implementing use of only a single vial from the 3-vial FIT screening kit would reduce the colonoscopy reflex rate, colonoscopy complication numbers, facility costs, and patient distress by more than 40%, compared with 3-vial screening.

scholarly journals Point Sensitivity of the Multi-target Stool DNA Test for Colorectal Cancer Screening in Individuals Ages 45-49 Years

2020 ◽  
Author(s):  
Michael Domanico ◽  
Sandra Statz ◽  
Emily Weiser ◽  
Barry M Berger ◽  
Paul J Limburg
Keyword(s):  
Colorectal Cancer ◽  
Precancerous Lesions ◽  
Screening Tests ◽  
Average Risk ◽  
Small Pilot Study ◽  
Data Annotation ◽  
Test Sensitivity ◽  
Link Type ◽  
Stool Samples ◽  
Stool Dna

Background: Most colorectal cancer (CRC) screening tests have not been rigorously studied in younger age groups. Aims: To estimate sensitivity of the multi-target stool DNA (mt-sDNA) test in patients ages 45-49 years. Methods: We identified archived stool samples (Exact Sciences; Madison, WI) from individuals ages 45-49 years who had completed an index colonoscopy and had confirmed diagnoses of CRC or advanced precancerous lesions (APL; defined as high-grade dysplasia, greater than 25% villous morphology, or greater than or equal to 1 cm in size [conventional adenoma or serrated lesion]). Data annotation referent to potential CRC risk factors, other than age, was limited. Stool samples were collected at least 7 days after the index colonoscopy, prior to lesion excision or treatment. Stool samples were processed and analyzed per established laboratory protocols for the mt-sDNA assay. Mt-sDNA test sensitivity for CRC, APL, and CRC+APL was estimated from the available sample set. Samples were collected from 2010-2013 (NCT01260168) and 2014-2017 (NCT02503631), with sample testing and analysis in 2019. Results: Stool samples were analyzed from 19 eligible subjects, 13 with CRC and 6 with APL. Estimated mt-sDNA test sensitivity for CRC, APL, and CRC+APL were 92%, 83%, and 89%, respectively. Conclusions: In this small pilot study using existing archived stool samples from subjects ages 45-49 years, mt-sDNA test sensitivity was similar to previously reported estimates for individuals ages greater than or equal to 50 years. These results support the application of mt-sDNA screening to average-risk patients beginning at age 45 years. Larger studies are needed to confirm and extend these findings.

scholarly journals Adenoma Characteristics and the Influence of Alcohol and Cigarette Consumption on the Development of Advanced Colorectal Adenomas

2020 ◽  
Vol 17 (22) ◽  
pp. 8296
Author(s):  
Maja Čebohin ◽  
Senka Samardžić ◽  
Ksenija Marjanović ◽  
Martina Tot Vesić ◽  
Kristina Kralik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Alcohol Consumption ◽  
Occult Blood ◽  
Faecal Occult Blood Test ◽  
Cross Sectional Study ◽  
Colorectal Adenomas ◽  
Screening Methods ◽  
Cross Sectional ◽  
National Programme ◽  
Advanced Adenomas

Background: Colorectal cancer (CRC), one of the leading public health problems worldwide, is a disease that can be prevented when it is detected in time. The objectives of this cross-sectional study were to investigate the characteristics of colorectal adenomas and whether alcohol consumption and cigarette smoking correlated with the development of advanced adenomas in participants in The National Programme for Early Detection of Colorectal Cancer (NP) in Osijek-Baranja County (OBC), Croatia. Methods: The screening methods were the guaiac Faecal Occult Blood Test (gFOBT), colonoscopy, histological analysis, and risk factor questionnaire. Results: The results showed the presence of adenomas in 136 men (57.4%) and 101 women (42.6%), p < 0.001. There was one adenoma in 147 (62%) most commonly located in sigmorect, in 86 (59%) participants, and 44 (18.6%) participants had multiple adenomas, most commonly found in multi loc, p < 0.001. According to size, 118 (49.8%) of all adenomas were between 0.1 and 0.9 cm, while adenomas of 3 cm 19 (8%) were the fewest, p < 0.001. There were 142 (59.9%) advanced adenomas. Conclusions: Adenoma development in the OBC population was correlated with predictors: adenoma size, high-grade dysplasia, smoking and alcohol consumption of 20 g per day. Non-smoking was found to be a health protective behaviour.

Prospective clinical study of circulating tumor cells for colorectal cancer screening.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 556-556 ◽  
Author(s):  
Wen-Sy Tsai ◽  
Ashish Nimgaonkar ◽  
Oscar Segurado ◽  
Ying Chang ◽  
Ben Hsieh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Study ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Precancerous Lesions ◽  
Specific Binding ◽  
Detection Methods ◽  
Prospective Clinical Study ◽  
Screening Methods ◽  
Blood Draw

556 Background: Colorectal cancer (CRC) is among the most preventable cancers when precancerous lesions are detected at an early stage. Current screening methods for CRC require bowel prep or stool-based testing that are inconvenient, resulting in low compliance. Stool based tests have limited sensitivity for the detection of precancerous lesions. We have conducted a prospective clinical study over a period of > 3 years to assess a novel assay to detect and enumerate circulating tumor cells (CTCs) in a blood sample for early CRC detection. Methods: A single-center, IRB-approved, prospective and blinded clinical study was conducted in 620 subjects including 438 with adenoma, polyps or stage I-IV CRC and 182 healthy controls. For each subject, 2mL peripheral whole blood collected through a routine blood draw was processed using the CellMax biomimetic platform (CMx). The CMx test is a proprietary microfluidic biochip that minimizes non-specific binding and accurately enumerates CTCs. A multivariate analysis was performed to assess the clinical performance characteristics of the CMx test. Results: Disease status was evaluated by a standard clinical protocol which included colonoscopy and biopsy results. Probability of CRC risk was assessed by an age-adjusted regression model which correlated CTCs to clinical status. The CMx test’s overall accuracy was 88% for all stages of colorectal illness, including precancerous lesions. Conclusions: The study has demonstrated high accuracy for the detection of CRC using a novel CTC assay. It is the first study to show high sensitivity in the detection of precancerous colorectal lesions. The simple blood draw required can be easily integrated into a patient’s routine physical, increasing test compliance.[Table: see text]

Lipidomics As Tools For Finding Biomarkers Of Intestinal Pathology: From Irritable Bowel Syndrome To Colorectal Cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Lorena Ortega Moreno ◽  
Pilar Navarro Sánchez ◽  
Raquel Abalo
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Bowel Disease ◽  
Screening Methods ◽  
Intestinal Diseases ◽  
Non Invasive ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Irritable Bowel

: Lipidomics is an emerging and promising branch that analyses the different lipid mole-cules in a biological sample. It is considered a branch of metabolomics, which is defined as the comprehensive analysis of metabolites in a biological specimen. Nonetheless, in recent years lipidomics is becoming a distinct discipline in the biomedicine field. Lipids play important roles in many biological pathways and can work as biomarkers of disease or therapeutic targets for the treatment of diseases. The major lipidomics strategies are shotgun lipidomics and liquid chromatography coupled with mass spectrometry. Gastro-intestinal diseases, such as irritable bowel syndrome or inflammatory bowel disease, are chronic diseases that need non-invasive biomarkers for prognosis and diagnosis. Even more, patients with inflammatory bowel disease are at significantly increased risk of colorectal cancer, principally resulting from the pro-neoplastic effects of chronic intesti-nal inflammation. Current screening methods utilized globally include sigmoidoscopy or standard colonoscopy, but it is important to develop non-invasive and accurate screen-ing tools to facilitate early detection and precise staging of colorectal cancer. Disease progression and response to treatment may also benefit from the application of these potential new tools. This review focuses on studies that use lipidomics approaches to discover potential biomarkers for monitoring the mentioned intestinal diseases and, par-ticularly, tumor progression.

scholarly journals Simultaneous Detection of Colorectal Cancer Mutations in Stool Samples with Biochip Arrays

2009 ◽  
Vol 28 (4) ◽  
pp. 285-292
Author(s):  
Helena Murray ◽  
Mark Latten ◽  
Andrew Cartwright ◽  
Damien McAleer ◽  
Stephen Fitzgerald
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Simultaneous Detection ◽  
Occult Blood ◽  
Western World ◽  
Non Invasive ◽  
Invasive Test ◽  
Cancer Mutations ◽  
Dna Alterations ◽  
Stool Samples

Simultaneous Detection of Colorectal Cancer Mutations in Stool Samples with Biochip ArraysColorectal cancer (CRC) is the second main cause of cancer-related death in the Western world and like many other tumours is curable if detected at an early stage. Current detection options include faecal occult blood testing and invasive direct visualisation techniques such as flexible sigmoidoscopy, colonoscopy and barium enema. The availability of a more simple, non-invasive test that detects tumour specific products with optimal analytical performance might overcome barriers among patients who are not willing to undergo more sensitive but invasive tests. One such emerging technology, which has shown promise in recent years, is the analysis of DNA alterations exfoliated from tumour cells into stool. Here we report an analytical platform for non-invasive detection of 28 common mutations within CRC-related genesAPC, TP53, K-rasandBRAFin stool samples based on biochip array technology and applied to the semi-automated Evidence Investigator analyser. Mutation detection was possible in 1000-fold excess of wildtype DNA and analysis of 10 CRC-positive patient samples showed presence of targeted mutations with equivalent mutations also identified by an alternative method. This application represents an excellent tool for the multiplex detection of CRC-specific mutations using a single platform.

scholarly journals Comparing Metabolomics Profiles in Various Types of Liquid Biopsies among Screening Participants with and without Advanced Colorectal Neoplasms

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 561
Author(s):  
Vanessa Erben ◽  
Gernot Poschet ◽  
Petra Schrotz-King ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Neoplasms ◽  
Urine Samples ◽  
Screening Colonoscopy ◽  
Liquid Biopsies ◽  
Blood Samples ◽  
Metabolite Concentrations ◽  
Stool Samples ◽  
Positive Correlations ◽  
Advanced Adenomas

Analysis of metabolomics has been suggested as a promising approach for early detection of colorectal cancer and advanced adenomas. We investigated and compared the metabolomics profile in blood, stool, and urine samples of screening colonoscopy participants and aimed to evaluate differences in metabolite concentrations between people with advanced colorectal neoplasms and those without neoplasms. Various types of bio-samples (plasma, feces, and urine) from 400 participants of screening colonoscopy were investigated using the MxP® Quant 500 kit (Biocrates, Innsbruck, Austria). We detected a broad range of metabolites in blood, stool, and urine samples (504, 331, and 131, respectively). Significant correlations were found between concentrations in blood and stool, blood and urine, and stool and urine for 93, 154, and 102 metabolites, of which 68 (73%), 126 (82%), and 39 (38%) were positive correlations. We found significant differences between participants with and without advanced colorectal neoplasms for concentrations of 123, 49, and 28 metabolites in blood, stool and urine samples, respectively. We detected mostly positive correlations between metabolite concentrations in blood samples and urine or stool samples, and mostly negative correlations between urine and stool samples. Differences between subjects with and without advanced colorectal neoplasms were found for metabolite concentrations in each of the three bio-fluids.

scholarly journals Highly-specific early detection of colorectal cancer by novel non-invasive serum methylation biomarkers

2021 ◽  
Author(s):  
Maria Gallardo-Gomez ◽  
Mar Rodriguez-Girondo ◽  
Nuria Planell ◽  
Sebastian Moran ◽  
Luis Bujanda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Serum Samples ◽  
Screening Programs ◽  
Non Invasive ◽  
Incidence And Mortality ◽  
Sample Pooling ◽  
Immunochemical Test ◽  
Advanced Adenomas

Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicentre cohort of 453 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC. First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new non-invasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test. Overall, our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.

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