Dataset Information

Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis.

ABSTRACT:

Background

Fecal immunochemical test (FIT), DNA mutation, DNA methylation, and microbial dysbiosis all showed promising in colorectal cancer (CRC) non-invasive detection. We assessed CRC detection with an assay combining all these strategies and investigated the effect of clinical features on the performance of this comprehensive test.

Methods

We performed a multidimensional analysis study using stool samples collected from 108 patients with CRC, 18 patients with colorectal adenoma, and 36 individuals with no evidence of colorectal disease. The multidimensional analysis of stool samples including FIT, stool DNA (sDNA) tests for three methylated genes (Septin9, NDRG4, BMP3) and three mutated genes (KRAS, BRAF, PI3KCA) using next generation sequencing as well as detection of stool bacteria level of Fusobacterium nucleatum and Parvimonas micra using qPCR method. We used a linear support vector classification model to analyze the data.

Results

The sensitivity of FIT alone was 69.4% for CRC and 11.1% for adenoma. Separately, the sensitivity of the detection of intestinal bacteria, DNA mutation, and DNA methylation for CRC was 58.3, 50.0, and 51.9%, respectively. The combination of FIT and sDNA tests had a sensitivity of 81.5% for CRC (AUC: 0.93, better than FIT alone, P = 0.017) and 27.8% for adenoma with 94.4% specificity. Sensitivity of the multidimensional test to detect CRC with stage II (84.6%) and III (91.9%) CRC was relatively higher (88.2%) than that of patients with stage I (60.0%) and stage IV (75.0%) (P = 0.024). The rate of CRC detection increased with tumor size (P = 0.008) and age (P = 0.04). Interestingly, the rate of CRC detection was higher in smoking persons than non-smokers with marginal significance (P = 0.08).

Conclusions

The multidimensional assay of stool samples combining FIT and stool DNA tests further improved the diagnostic sensitivity for CRC. This could provide new approach for improvement of CRC screening and further demonstrations are warranted.

SUBMITTER: Mo S

PROVIDER: S-EPMC7947614 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis.

Mo Shaobo S Wang Hui H Han Lingyu L Xiang Wenqiang W Dai Weixing W Zhao Pengfei P Pei Fengchun F Su Zhixi Z Ma Chengcheng C Li Qi Q Wang Zhimin Z Cai Sanjun S Wang Hao H Liu Rui R Cai Guoxiang G

Frontiers in oncology 20210225

<h4>Background</h4>Fecal immunochemical test (FIT), DNA mutation, DNA methylation, and microbial dysbiosis all showed promising in colorectal cancer (CRC) non-invasive detection. We assessed CRC detection with an assay combining all these strategies and investigated the effect of clinical features on the performance of this comprehensive test.<h4>Methods</h4>We performed a multidimensional analysis study using stool samples collected from 108 patients with CRC, 18 patients with colorectal adenom ...[more]

PMID: 33718241

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Project description:BackgroundMany screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program.MethodThe mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants.DiscussionThe outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening.Trial registrationClinicaltrials.gov ; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist =.

Project description:BackgroundColonoscopy surveillance intervals are based on the predicted risk of metachronous colorectal cancer (CRC) after polyp removal. However, risk estimation per polyp subtype is difficult due to the fact that many patients have multiple polyps. To enable risk estimation per polyp subtypes we examined the metachronous CRC risk of subgroups based on presence or absence of co-occurring findings.MethodsUsing high-quality screening colonoscopies performed after a positive fecal immunochemical test between 2014 and 2020 within the Dutch CRC screening program, we applied Cox regression analysis to evaluate the association between findings at baseline colonoscopy and metachronous CRCs. For our primary outcome, we appointed each patient to unique subgroups based on removed polyp subtypes that were present or absent at baseline colonoscopy and used the groups without polyps as reference. High-risk subgroups were individuals with high-risk serrated polyps, defined as serrated polyp ≥10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, defined as adenoma ≥10 mm or containing high-grade dysplasia.FindingsIn total 253,833 colonoscopies were included. Over a median follow-up of 36 months (IQR, 21-57), we identified 504 metachronous CRCs. Hazard ratios for metachronous CRC was 1.70 (95% CI, 1.07-2.69) for individuals with high-risk serrated polyps without high-risk adenomas, 1.22 (0.96-1.55) for individuals with high-risk adenomas without high-risk serrated polyps, and 2.00 (1.19-3.39) for individuals with high-risk serrated polyps and high-risk adenomas, compared to patients without polyps.InterpretationAccounting for co-occurring findings, we observed an increased metachronous CRC risk for individuals that had high-risk serrated polyps with the presence of high-risk adenomas, or individuals with high-risk serrated polyps without high-risk adenomas. These findings could provide more evidence to support post-polypectomy surveillance guidelines.FundingNone.

Dataset Information

Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis.

Background

Methods

Results

Conclusions

Publications

Fecal Multidimensional Assay for Non-Invasive Detection of Colorectal Cancer: Fecal Immunochemical Test, Stool DNA Mutation, Methylation, and Intestinal Bacteria Analysis.

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