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 Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 437
Author(s):  
Olalla Otero-Estévez ◽  
María Gallardo-Gomez ◽  
María Páez de la Cadena ◽  
Francisco Javier Rodríguez-Berrocal ◽  
Joaquín Cubiella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Family Risk ◽  
Liquid Biopsies ◽  
Age And Gender ◽  
Screening Programs ◽  
Aberrant Dna Methylation ◽  
And Gender ◽  
Asymptomatic Individuals ◽  
Advanced Adenomas

Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia—AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35–47% AA (specificity 98–95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals.

scholarly journals Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 16
Author(s):  
Saray Duran-Sanchon ◽  
Elena Vila-Navarro ◽  
Maria Marcuello ◽  
Juan José Lozano ◽  
Jenifer Muñoz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Research Field ◽  
Circulating Microrna ◽  
Endogenous Control ◽  
Serum Samples ◽  
Liquid Biopsies ◽  
Circulating Mirna ◽  
Polymerase Chain ◽  
Advanced Adenomas ◽  
Colorectal Cancer Patients

Background: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in the colorectal cancer (CRC) context whereas several have been suggested. Hence, our aims were to validate the previously suggested miR-1228-3p as HK for CRC studies, to compare its suitability with the widely used miR-16-5p, and to evaluate the influence of hemolysis on both miRNAs. Methods: We analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) the expression of miR-1228-3p, miR-16-5p and the spike-in cel-miR-39 in a set of 297 plasmas (92 CRC, 101 advanced adenomas -AA-, and 100 controls) and 213 serum samples (59 CRC, 74 AA and 80 controls). We also analyzed both miRNAs depending on the hemolysis degree in 7 plasmas and 31 serums. Results: Levels of miR-1228-3p and miR-16-5p did not show significant differences between groups although miR-16-5p exhibited more variability in plasma and serum samples. Importantly, the combination of cel-miR-39 and miR-1228-3p was the most stable one. Moreover, we observed that miR-16-5p was significantly influenced by hemolysis in contrast with miR-1228-3p that exhibited no correlation with this confounding factor in both biofluids. Conclusion: MiR-1228-3p has been validated as an adequate endogenous control for circulating miRNA analysis in CRC and AA liquid biopsies.

scholarly journals A prospective study of faecal immunochemical testing following polypectomy in a colorectal cancer screening population

2017 ◽  
Vol 9 (4) ◽  
pp. 295-299 ◽  
Author(s):  
David J Gibson ◽  
Blathnaid Nolan ◽  
Joanna Rea ◽  
Maire Buckley ◽  
Gareth Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Screening Programme ◽  
Clinical Findings ◽  
Adenomatous Polyps ◽  
Screening Colonoscopy ◽  
Cancer Screening Programme ◽  
Advanced Adenomas

Introduction52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT.AimsDetermine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up.MethodsA single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4–6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention.Results112 consecutive first round participants were recruited. Eight (7%) had cancer, 75 (67%) adenomatous polyps, 17 (15%) a normal colonoscopy and 12 (11%) other pathology. There was a clear difference in median FIT levels between the four groups (P=0.006). Advanced pathology (tumour or adenomatous polyp >1 cm) was associated with higher FIT than non-advanced pathology (median FIT 346 vs 89 P=0.0003). 83% (86/104) of subjects completed a follow-up FIT. Follow-up FIT remained positive in 20% (17/86). Polypectomy was associated with a reduction in FIT from a median of 100 to 5 µg Hb/g (P<0.0001). Removal of polyps >5 mm was the only factor independently associated with a negative follow-up FIT on multivariate analysis (OR 3.9 (1.3–11.9, P=0.04)).ConclusionFIT is a sensitive test and levels increase with advanced colonic pathology. Polypectomy of advanced adenomas is associated with a negative follow-up FIT. However, alternative causes for a positive FIT should be considered in patients who have adenomas less than 5 mm detected or a normal colonoscopy.

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.

Gender Specific Prevalence of Adenomas, Advanced Adenomas, and Colorectal Cancer in Patients Undergoing Screening Colonoscopy

2012 ◽  
Vol 107 ◽  
pp. S815
Author(s):  
Rajan Kochar ◽  
Praveen Guturu ◽  
Sarat Jampana ◽  
Bashar Hmoud ◽  
Habeeb Salameh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Screening Colonoscopy ◽  
Advanced Adenomas ◽  
Gender Specific

Prospective clinical study using expressed sequencing variants on stool-derived eukaryotic RNA transcripts (seRNA) for colorectal cancer screening.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 516-516
Author(s):  
Erica Kay Barnell ◽  
Yiming Kang ◽  
Katie Marie Campbell ◽  
Andrew Ross Barnell ◽  
Kimberly Ray Kruse ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Study ◽  
The United States ◽  
Screening Colonoscopy ◽  
Noninvasive Evaluation ◽  
Prospective Clinical Study ◽  
Acid Extraction ◽  
Screening Guidelines ◽  
Mutational Burden ◽  
Advanced Adenomas

516 Background: Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. The high mortality rate is largely attributable to the high frequency of late-stage diagnoses, caused by low patient compliance with screening guidelines. A reliable and noninvasive screening alternative is needed for the 40 million noncompliant patients. The development of a novel nucleic acid extraction method to isolate stool-derived eukaryotic RNA (seRNA) permits reliable and noninvasive evaluation of biomarkers derived from the gastrointestinal (GI) epithelium. This method enables sequencing-based tools for the detection of patients with CRC and adenomas. Methods: Stool samples were obtained from 96 individuals prior to undergoing a screening colonoscopy. Fecal immunochemical tests (FITs) were obtained for each sample. RNA isolates underwent custom library preparation, next-generation sequencing, and somatic variant identification. An seRNA assay assessed the probability of CRC risk using results from the FIT, mutational burden of transcripts implicated in precancerous change (APC), and mutational burden of transcripts associated with malignant transformation (KRAS / TP53). Results: When compared to results from a colonoscopy and subsequent biopsy, the seRNA risk assessment attained a 100% sensitivity for CRC, a 71.4% sensitivity for advanced adenomas, and an 88.5% specificity for no neoplastic findings. Conclusions: A single-center, IRB-approved, prospective and blinded clinical study is being conducted in 450 patients to further develop this seRNA assay. Supplemental data will include expression from 408 seRNA transcripts. Preliminary analysis described herein indicates this assay could be the most sensitive noninvasive screening test for the detection of CRC and adenomas. [Table: see text]

scholarly journals Multiple Biomarker-Combined Screening for Colorectal Cancer Based on Bisulfate Conversion-Free Detection of Fecal DNA Methylation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chong Liu ◽  
Lei Xu ◽  
Wei Li ◽  
Min Jie ◽  
Wei Xue ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Enzyme Digestion ◽  
Detection Sensitivity ◽  
Clinical Samples ◽  
Crc Screening ◽  
Methylation Assay ◽  
Multiple Biomarkers ◽  
Stool Samples ◽  
Advanced Adenomas

To evaluate the applicability of bisulfate conversion-free methylation assay based on enzyme digestion in fecal screening for colorectal cancer (CRC). Stool samples were collected from a total of 1142 participants with intestinal abnormalities, including 180 positive cases, 60 advanced adenomas, and 902 negative cases. DNA from reference cell lines and clinical samples was extracted and digested with an enzyme to detect the methylation of CRC markers SEPT9, SDC2, NDRG4, SFRP2, and BMP3 genes. Statistical analysis was then used to determine the ability of the markers, both individually and in combination, to detect CRC and adenoma. Our results showed that the enzyme digestion method could suitably detect DNA marker methylation in as low as 1% of the cell lines. BMP3 had a considerably low detection rate in all clinical samples, with only 6 positive cases detected out of 180 cancer samples. Our findings showed that the combination of SEPT9, SDC2, and SFRP2 had an area under the receiver operation curve of 0.937, sensitivity of 94.11%, and specificity of 89.21% for detecting CRC. Moreover, the detection sensitivity of adenoma can also reach 38.33%. After innovatively utilizing bisulfate conversion-free methylation assay for CRC screening, this study verified the potential clinical applicability of combining multiple biomarkers for CRC screening in a large number of samples.

scholarly journals Faecal Diagnostic Biomarkers for Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5568
Author(s):  
Andrea Cruz ◽  
Carla M. Carvalho ◽  
Alexandra Cunha ◽  
Anais Crespo ◽  
Águeda Iglesias ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Occult Blood ◽  
Diagnostic Value ◽  
Necrosis Factor Alpha ◽  
Diagnostic Biomarkers ◽  
Advanced Stages ◽  
Immunochemical Test ◽  
Stool Samples ◽  
Advanced Adenomas

Background: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. Current methods for CRC screening commonly consist of a combination of faecal immunochemical test (FIT) for stool occult blood detection and invasive procedures such as colonoscopy. Considering the slow progression of CRC, and that symptoms usually emerge at advanced stages, its early diagnostic can limit cancer’s spread and provide a successful treatment. Biomarkers have a high potential for the diagnosis of CRC in either blood or stool samples. Methods: In this study, we analysed the diagnostic value of six different biomarkers in stool samples of patients with CRC, advanced adenomas, other lesions and healthy individuals. We have also assessed the overall performance of the combination of these biomarkers for CRC detection. Results: The results indicate that haemoglobin (Hb) and M2-pyruvate kinase (M2-PK) levels were increased in CRC patients in comparison to the controls. Conversely, the concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and tumour necrosis factor-alpha (TNF-α) were not significantly different between the tested groups. Conclusion: The combination of FIT-Hb with the M2-PK levels increased the specificity or sensitivity for CRC detection and thus present potential as faecal diagnostic biomarkers for CRC.

scholarly journals Impact of restrictions due to COVID-19 on a quality-assured screening colonoscopy program

2021 ◽  
Vol 09 (09) ◽  
pp. E1315-E1320
Author(s):  
Anna Hinterberger ◽  
Lena Jiricka ◽  
Elisabeth A. Waldmann ◽  
Daniela Penz ◽  
Barbara Majcher ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Screening Program ◽  
Screening Colonoscopy ◽  
Rank Test ◽  
Chi Square ◽  
Period 2 ◽  
Cancer Screening Program ◽  
Chi Square Test ◽  
Advanced Adenomas ◽  
The Impact

Abstract Background and study aims On February 25, 2020, the first patient was diagnosed with COVID-19 in Austria. On March 16, 2020, the Austrian government imposed restrictions and subsequently the Austrian Medical Association recommended minimizing screening examinations in compliance with government restrictions. The aims of this study were to evaluate the impact of this recommendation on the number of colonoscopies performed weekly and detection of non-advanced adenomas, advanced adenomas (AA) and colorectal cancer (CRC) and to calculate how many undetected adenomas could have developed into CRC. Methods We analyzed the number of colonoscopies and pathological findings within a quality assured national colorectal cancer screening program before the COVID-19 pandemic (March 1,t 2019 to September 1, 2019, Period 1) and compared those rates to months during which access to colonoscopy was limited (March 1, 2020 and September 1, 2020, Period 2) with a Wilcoxon-rank-test and a chi-square test. Results A total of 29,199 screening colonoscopies were performed during Period 1 and 24,010 during Period 2. The mean rate of colonoscopies per week during Period 1 was significantly higher than during Period 2 (808,35 [SD = 163,75] versus 594,50 [SD = 282,24], P = 0.005). A total of 4,498 non-advanced adenomas were detected during Period 1 versus 3,562 during Period 2 (P < 0.001). In total 1,317 AAs and 140 CRCs were detected during Period 1 versus 919 AAs and 106 CRCs during Period 2. These rates did not differ significantly (P = 0.2 and P = 0.9). Conclusions During the COVID-19 crisis, the number of colonoscopies performed per week was significantly lower compared to the year before, but there was no difference in the detection of CRCs and AAs.

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