Evaluation of a 92 multiplex protein panel in detection of colorectal cancer and high-risk adenoma in 784 symptomatic individuals

2021 ◽  
pp. 1-12
Author(s):  
Louise Rasmussen ◽  
Hans Jørgen Nielsen ◽  
Ib Jarle Christensen
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Colorectal Adenoma ◽  
Precancerous Lesions ◽  
Protein Profiling ◽  
Superior Performance ◽  
Full Potential ◽  
Protein Biomarkers ◽  
Proximity Extension Assay ◽  
Control Study

BACKGROUND: Blood-based protein biomarkers for detection of colorectal cancer (CRC) have been submitted to intense research to improve the full potential in screening for CRC. OBJECTIVE: The aim was to explore the diagnostic performance of 92 proteins related to inflammation and carcinogenesis in detection of CRC or precancerous lesions. METHODS: Blood-samples were collected from 4,698 individuals undergoing colonoscopy. An explorative unmatched case-control study was designed with 294 cases (individuals with CRC or high-risk colorectal adenoma) and 490 controls (individuals with low-risk colorectal adenoma, non-malignant findings or clean colorectum at colonoscopy). Protein profiling was performed by multiplex proximity extension assay. Statistical analyses were performed as univariate and multivariate logistic regression analyses. RESULTS: Univariably, CSF-1, MMP12 and IL8 demonstrated superior performance in discrimination of individuals with CRC. Recurrently, IL8 was included as contributor in majority of multivariate models discriminating individuals with CRC. The multivariate evaluation in discrimination of individuals with CRC demonstrated AUC=ROC 0.82, sensitivity = 0.39 at specificity = 0.80. Discrimination of individuals with late stage CRC from individuals with clean colorectum demonstrated AUC=ROC 0.90, sensitivity = 0.58 at specificity = 0.80. CONCLUSIONS: A subset of biomarker candidates, specifically IL8, investigated in the present study suggest a potential as blood-based biomarkers in screening of CRC.

Risk of Colorectal Cancer After Detection and Removal of Adenomas at Colonoscopy: Population-Based Case-Control Study

2012 ◽  
Vol 30 (24) ◽  
pp. 2969-2976 ◽  
Author(s):  
Hermann Brenner ◽  
Jenny Chang-Claude ◽  
Alexander Rickert ◽  
Christoph M. Seiler ◽  
Michael Hoffmeister
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Risk Reduction ◽  
Large Bowel ◽  
Case Control Study ◽  
Significant Risk ◽  
Population Based ◽  
Case Control ◽  
Odds Ratios ◽  
Control Study

Purpose Empirical evidence for recommendations of surveillance intervals after detection and removal of adenomas at colonoscopy is still sparse and mostly based on observations of adenoma recurrence. We aimed to assess risk of colorectal cancer (CRC) according to time since polypectomy and factors that might be relevant for risk stratification. Methods In a population-based case-control study conducted in Germany, detailed history and results of previous large-bowel endoscopies were obtained by interview and from medical records. Risk of CRC among participants with detection of at least one adenoma at a preceding colonoscopy compared with participants without previous large-bowel endoscopy was assessed according to time since polypectomy among 2,582 cases with CRC and 1,798 matched controls. Results Adjusted odds ratios (95% CIs) of CRC for participants with polypectomy less than 3, 3 to 5, and 6 to 10 years ago (using participants without previous endoscopy as reference group) were 0.2 (0.2 to 0.3), 0.4 (0.3 to 0.6), and 0.9 (0.5 to 1.5), respectively. Strong, significant risk reduction within 5 years was consistently seen for women and men, younger and older participants, patients with and without high-risk polyps (three or more polyps, at least one polyp ≥ 1 cm, at least one polyp with villous components), and those with and without polypectomy in the right colon. With adjusted odds ratios of 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.5) and 0.4 (0.2 to 0.8) for patients with polypectomy less than 3, 3 to 5, and 6 to 10 years ago, risk reduction was particularly strong for left-sided CRC. Conclusion Extension of surveillance intervals to 5 years should be considered, even after detection and removal of high-risk polyps.

Circulating tumor DNA methylation profiles enable early diagnosis, prognosis prediction, and screening for colorectal cancer

2020 ◽  
Vol 12 (524) ◽  
pp. eaax7533 ◽  
Author(s):  
Huiyan Luo ◽  
Qi Zhao ◽  
Wei Wei ◽  
Lianghong Zheng ◽  
Shaohua Yi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prediction Model ◽  
Prospective Cohort ◽  
Learning Algorithm ◽  
Precancerous Lesions ◽  
Circulating Tumor Dna ◽  
High Risk Population ◽  
Tumor Dna ◽  
Normal Controls

Circulating tumor DNA (ctDNA) has emerged as a useful diagnostic and prognostic biomarker in many cancers. Here, we conducted a study to investigate the potential use of ctDNA methylation markers for the diagnosis and prognostication of colorectal cancer (CRC) and used a prospective cohort to validate their effectiveness in screening patients at high risk of CRC. We first identified CRC-specific methylation signatures by comparing CRC tissues to normal blood leukocytes. Then, we applied a machine learning algorithm to develop a predictive diagnostic and a prognostic model using cell-free DNA (cfDNA) samples from a cohort of 801 patients with CRC and 1021 normal controls. The obtained diagnostic prediction model discriminated patients with CRC from normal controls with high accuracy (area under curve = 0.96). The prognostic prediction model also effectively predicted the prognosis and survival of patients with CRC (P < 0.001). In addition, we generated a ctDNA-based molecular classification of CRC using an unsupervised clustering method and obtained two subgroups of patients with CRC with significantly different overall survival (P = 0.011 in validation cohort). Last, we found that a single ctDNA methylation marker, cg10673833, could yield high sensitivity (89.7%) and specificity (86.8%) for detection of CRC and precancerous lesions in a high-risk population of 1493 participants in a prospective cohort study. Together, our findings showed the value of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of CRC.

scholarly journals Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Minsuk Kim ◽  
Emily Vogtmann ◽  
David A. Ahlquist ◽  
Mary E. Devens ◽  
John B. Kisiel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Colorectal Adenoma ◽  
Precancerous Lesions ◽  
Colorectal Adenomas ◽  
Advanced Adenoma ◽  
Bioactive Lipids ◽  
Gut Microbes ◽  
Cancer Pathogenesis ◽  
Composition Profiles

ABSTRACT Colorectal adenomas are precancerous lesions of colorectal cancer (CRC) that offer a means of viewing the events key to early CRC development. A number of studies have investigated the changes and roles of gut microbiota in adenoma and carcinoma development, highlighting its impact on carcinogenesis. However, there has been less of a focus on the gut metabolome, which mediates interactions between the host and gut microbes. Here, we investigated metabolomic profiles of stool samples from patients with advanced adenoma (n = 102), matched controls (n = 102), and patients with CRC (n = 36). We found that several classes of bioactive lipids, including polyunsaturated fatty acids, secondary bile acids, and sphingolipids, were elevated in the adenoma patients compared to the controls. Most such metabolites showed directionally consistent changes in the CRC patients, suggesting that those changes may represent early events of carcinogenesis. We also examined gut microbiome-metabolome associations using gut microbiota profiles in these patients. We found remarkably strong overall associations between the microbiome and metabolome data and catalogued a list of robustly correlated pairs of bacterial taxa and metabolomic features which included signatures of adenoma. Our findings highlight the importance of gut metabolites, and potentially their interplay with gut microbes, in the early events of CRC pathogenesis. IMPORTANCE Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., the collection of microbes residing in our gut, has been recognized as a key player in CRC development. There have been a number of gut microbiota profiling studies for colorectal adenoma and CRC; however, fewer studies have considered the gut metabolome, which serves as the chemical interface between the host and gut microbiota. Here, we conducted a gut metabolome profiling study of colorectal adenoma and CRC and analyzed the metabolomic profiles together with paired microbiota composition profiles. We found several chemical signatures of colorectal adenoma that were associated with some gut microbes and potentially indicative of future CRC. This study highlights potential early-driver metabolites in CRC pathogenesis and guides further targeted experiments and thus provides an important stepping stone toward developing better CRC prevention strategies.

scholarly journals Serum homocysteine may related to colorectal adenoma number: a cross-sectional study

2020 ◽  
Author(s):  
Jing-Wei Wang ◽  
Ya-Dan Wang ◽  
Jing Wu ◽  
Feng-Xiao Dong ◽  
Lin Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Colorectal Adenoma ◽  
Intraepithelial Neoplasia ◽  
Serum Levels ◽  
High Serum ◽  
Serum Biomarkers ◽  
Cross Sectional ◽  
Colon Adenomas ◽  
Serum Homocysteine

Abstract BackgroundEarly detection of high-risk adenomas is crucial for the prevention of colorectal cancer. The aim of the study was to evaluate the usefulness of serum biomarkers in characterizing the histological features of colon adenomas and predicting the progression of high-risk adenomas to colorectal cancer.MethodsPatients diagnosed with colorectal adenoma in Beijing Shijitan Hospital between Jan 2013 and Dec 2015 were recruited to the study. Patients were classified into low-, moderate-, and high-risk according to the adenoma scores. Erythrocyte sedimentation rate (ESR), clinical biochemistry, serum homocysteine (HCY) levels, and serum tumor markers were determined. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. The correlation between the serum biomarkers and basic characteristic of the adenomas was analyzed.ResultsThe serum levels of HCY (OR=0.06, 95% CI 0.01-1.52), CA724 (OR=0.03, 95% CI 0.00-0.97), and ESR (OR=0.01, 95% CI 0.00-0.44) were positively correlated with the risk of colon adenomas developing into colorectal cancers. High serum level of HCY was related with the development of multiple (>3) adenomas (OR=0.25, 95% CI 0.11-0.56). Higher ESR was related to the occurrence of high-grade intraepithelial neoplasia (OR=0.06, 95% CI 0.00-0.73) and villous adenomas (OR=0.20, 95% CI 0.04-0.98).ConclusionSerum levels of HCY, ESR and CA724 may be valuable indicators for predicting the risk of colon adenomas, among them, ESR may be more related to specific pathology types, HCY is more related to the number of adenomas and development of colorectal cancer.

scholarly journals Comparison of Proteomic Technologies for Blood-Based Detection of Colorectal Cancer

2021 ◽  
Vol 22 (3) ◽  
pp. 1189
Author(s):  
Megha Bhardwaj ◽  
Tobias Terzer ◽  
Petra Schrotz-King ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Multiple Reaction Monitoring ◽  
Area Under The Curve ◽  
Superior Performance ◽  
Blood Protein ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Functional Protein ◽  
Novel Technologies ◽  
Diagnostic Potential

Blood-based protein biomarkers are increasingly being explored as supplementary or efficient alternatives for population-based screening of colorectal cancer (CRC). The objective of the current study was to compare the diagnostic potential of proteins measured with different proteomic technologies. The concentrations of protein biomarkers were measured using proximity extension assays (PEAs), liquid chromatography/multiple reaction monitoring–mass spectrometry (LC/MRM-MS) and quantibody microarrays (QMAs) in plasma samples of 56 CRC patients and 99 participants free of neoplasms. In another approach, proteins were measured in serum samples of 30 CRC cases and 30 participants free of neoplasm using immunome full-length functional protein arrays (IpAs). From all the measurements, 9, 6, 35 and 14 protein biomarkers overlapped for comparative evaluation of (a) PEA and LC/MRM-MS, (b) PEA and QMA, (c) PEA and IpA, and (d) LC/MRM-MS and IpA measurements, respectively. Correlation analysis was performed, along with calculation of the area under the curve (AUC) for assessing the diagnostic potential of each biomarker. DeLong’s test was performed to assess the differences in AUC. Evaluation of the nine biomarkers measured with PEA and LC/MRM-MS displayed correlation coefficients >+0.6, similar AUCs and DeLong’s p-values indicating no differences in AUCs for biomarkers like insulin-like growth factor binding protein 2 (IGFBP2), matrix metalloproteinase 9 (MMP9) and serum paraoxonase lactonase 3 (PON3). Comparing six proteins measured with PEA and QMA showed good correlation and similar diagnostic performance for only one protein, growth differentiation factor 15 (GDF15). The comparison of 35 proteins measured with IpA and PEA and 14 proteins analyzed with IpA and LC/MRM-MS revealed poor concordance and comparatively better AUCs when measured with PEA and LC/MRM-MS. The comparison of different proteomic technologies suggests the superior performance of novel technologies like PEA and LC/MRM-MS over the assessed array-based technologies in blood-protein-based early detection of CRC.

scholarly journals Do people change their diet after colorectal adenoma diagnosis?

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Abeir El Mogassabi ◽  
Elizabeth Williams ◽  
Bernard Corfe ◽  
Mark Hull
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Dietary Intake ◽  
Colorectal Adenoma ◽  
Daily Intake ◽  
Colorectal Adenomas ◽  
Alcoholic Beverages ◽  
Dietary Behaviour ◽  
Dietary Analysis ◽  
Adenoma Recurrence

AbstractColorectal cancer (CRC) is the fourth most common cancer in the UK; 95% of CRCs develop from colorectal adenomas. Adults in England aged 60–74 years are screened for colorectal cancer through the national Bowel Cancer Screening Programme (BCSP) which aims to detect colorectal cancer early, and also remove colorectal adenomas. However, adenoma recurrence is common. The World Cancer Research Fund (WCRF) estimates that around 45% of CRC cases could be prevented by a healthy lifestyle. There are no specific dietary guidelines to protect against adenoma recurrence and patients do not receive dietary advice in the care pathway. Nonetheless understanding the dietary intake of people with adenoma who are at high-risk of developing CRC and their subsequent dietary behaviour post-diagnosis may design future intervention strategies.This study aims to describe the diet of colorectal adenoma patients and evaluate whether there were elective changes in diet following diagnosis.The data used in this study were obtained from colorectal adenoma patients at high risk of recurrence, recruited to the seAFOod polyp prevention trial through the English BCSP. Dietary intake was assessed using the EPIC Food Frequency Questionnaire at two time points: during the 12 months before and during the 12 months after adenoma diagnosis. FETA dietary analysis software was used to extract data. Paired Sample-T-Tests and Wilcoxon Signed-Rank Test were used to assess change in intake using SPSS version 25.Of the 709 patients recruited to the main study, 526 completed the FFQ on both occasions, of whom 81.7% were males. The mean age was 65 years (SD 4.8), 83.4% were overweight or obese with mean BMI = 29.5 kg/m2 (SD 5.7). The majority of nutrient intakes met UK DRVs, with the exception of low intake of fibre, vitamin D and selenium. Following diagnosis, a significant reduction was detected in daily intake of energy (from 7.7 to 7.5 MJ, p < 0.05) meat and meat products (from 124 to 111 g, p < 0.005), non-alcoholic beverages (from 939 to 898 g, p < 0.05) and nuts (from 5.5 to 4.3 g, p < 0.05). Subgroup analysis revealed that dietary changes were confined to men where the reduction in energy was by 293 kj/day and in meat by 1.5 portions per week.Patients do modify diet following a diagnosis of adenoma and changes correspond to WCRF healthy diet guidelines. Whether detected difference between males and females was due to the sample size or due to actual difference in behavior is not clear.

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