scholarly journals Evaluation and Validation of Plasma Proteins Using Two Different Protein Detection Methods for Early Detection of Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1426 ◽  
Author(s):  
Megha Bhardwaj ◽  
Anton Gies ◽  
Korbinian Weigl ◽  
Kaja Tikk ◽  
Axel Benner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Plasma Proteins ◽  
Multiple Reaction Monitoring ◽  
Protein Detection ◽  
Detection Methods ◽  
Screening Colonoscopy ◽  
Receptor Protein ◽  
Advanced Adenoma ◽  
Independent Validation

Objective: Plasma protein biomarkers could be an efficient alternative for population-based screening for early detection of colorectal cancer (CRC). The objective of this study was to evaluate and validate plasma proteins individually and as a signature for early detection of CRC. Methods: In a three-stage design, proteins were measured firstly by liquid chromatography/multiple reaction monitoring-mass spectrometry (LC/MRM-MS) and later by proximity extension assay (PEA) in a discovery set consisting of 96 newly diagnosed CRC cases and 94 controls free of neoplasms at screening colonoscopy. Two algorithms (one for each measurement method) were derived by Lasso regression and .632+ bootstrap based on 11 proteins that were included in both the LC/MRM-MS and PEA measurements. Additionally, another algorithm was constructed from the same eleven biomarkers plus amphireglin, the most promising protein marker in the PEA measurements that had not been available from the LC/MRM-MS measurements. Lastly the three prediction signatures were validated with PEA in independent samples of participants of screening colonoscopy (CRC (n = 56), advanced adenoma (n = 101), and participants free of neoplasm (n = 102)). Results: The same four proteins were included in all three prediction signatures; mannan binding lectin serine protease 1, osteopontin, serum paraoxonase lactonase 3 and transferrin receptor protein 1, and the third prediction signature additionally included amphiregulin. In the independent validation set from a true screening setting, the five-marker blood-based signature including AREG presented areas under the curves of 0.82 (95% CI, 0.74–0.89), 0.86 (95% CI, 0.77–0.92) and 0.76 (95% CI, 0.64–0.86) for all, early and late stages CRC, respectively. Conclusion: Two different measurement methods consistently identified four protein markers and an algorithm additionally including amphiregulin, a marker measured by PEA only, showed promising performance for detecting early stage CRC in an independent validation in a true screening setting. These proteins may be potential candidates for blood-based tests for early detection of CRC.

scholarly journals Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Woo Kim ◽  
Hyunjin Kim ◽  
Hyoung Rae Kim ◽  
Bong-Hyeon Kye ◽  
Hyung Jin Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Detection ◽  
Prospective Trial ◽  
Screening Colonoscopy ◽  
Quantitative Detection ◽  
Screening Programs ◽  
Crc Screening ◽  
Stool Dna ◽  
Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

Use of RNA isolated from feces as a promising tool for the early detection of colorectal cancer

2012 ◽  
Vol 27 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Giuliano Bernal
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Low Cost ◽  
Occult Blood ◽  
Detection Methods ◽  
Fecal Occult Blood ◽  
Public Health Services ◽  
Promising Alternative ◽  
Altered Expression ◽  
Fecal Occult

Colorectal cancer is one of the most common forms of cancer worldwide. Early detection would allow patients to be treated surgically and halt the progression of the disease; however, the current methods of early detection are invasive (colonoscopy and sigmoidoscopy) or have low sensitivity (fecal occult blood test). The altered expression of genes in stool samples of patients with colorectal cancer can be determined by RT-PCR. This is a noninvasive and highly sensitive technique for colorectal cancer screening. According to information gathered in this review and our own experience, the use of fecal RNA to determine early alterations in gene expression due to malignancy appears to be a promising alternative to the current detection methods and owing to its low cost could be implemented in public health services.

scholarly journals Combination of Different Fecal Immunochemical Tests in Colorectal Cancer Screening: Any Gain in Diagnostic Performance?

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 120 ◽  
Author(s):  
Anton Gies ◽  
Katarina Cuk ◽  
Petra Schrotz-King ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Colorectal Cancer Screening ◽  
Diagnostic Performance ◽  
Screening Colonoscopy ◽  
Advanced Adenoma ◽  
Positive Test Result ◽  
Advanced Neoplasm ◽  
Test Result ◽  
Pairwise Test

A variety of fecal immunochemical tests (FITs) are used for colorectal cancer screening. FIT performance could be improved further. It is unclear, whether the combination of different FITs with different analytical characteristics (such as, different antibodies for the detection of fecal hemoglobin) can yield a better diagnostic performance. Fecal samples were obtained from 2042 participants of screening colonoscopy. All participants with advanced neoplasm (AN, colorectal cancer (n = 16) or advanced adenoma (n = 200)) and 300 randomly selected participants without AN were included. Nine quantitative FITs were evaluated simultaneously. Sensitivity and specificity was calculated for single tests (n = 9) and for their pairwise test combinations (n = 36) (requiring either both FITs (P++) or at least one FIT (P+) to be positive for defining a positive test result). Mean age of the participants (n = 516) was 63 (range: 50–79) years and 56% were men. At cutoffs yielding a specificity of 96.7% for single FITs, the median gain in specificity by P++ combination was +1.0%, whereas the median loss in sensitivity for AN was −4.2%. For P+ combination the median gain in sensitivity for AN was +2.8%, at a prize of median loss of −1.0% of specificity. Combinations of different FITs do not yield any relevant gain in diagnostic performance.

Detector-C 2.0: A highly accurate blood-based IVD test for early detection of colorectal cancer with sensitivity and specificity over 90%.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 393-393 ◽  
Author(s):  
Andre Rosenthal ◽  
Tobias Mayr ◽  
Hartmut Koeppen ◽  
Reiner Musikowski ◽  
Johannes Berendt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Case Control Study ◽  
Gene Selection ◽  
White Blood Cells ◽  
Case Control ◽  
Tumor Formation ◽  
Screening Colonoscopy ◽  
Support Vector ◽  
Control Study

393 Background: We previously reported on the discovery and prospective validation of a blood based test (Detector C) for early detection of colorectal cancer (CRC). Detector C measures 202 RNA markers in white blood cells as a response of the host to tumor formation and growth. Detector C was validated using a prospective, multicenter case-control study with 343 patients (pts), 210 cases with confirmed CRC and 133 controls undergoing a complete screening colonoscopy. Detector C has a validated sensitivity (S+) of 90% (95% CI 0.851-0.937) and specificity (S-) of 88% (95% CI 0.812-0.930) (Rosental A. et al, J Clin Oncol 28:7s, 2010 (suppl; abstr 3580)). We now present the discovery of Detector C 2.0 based on 445 samples representing most of the pts previously used in the discovery and validation sets of Detector C. Methods: We used Affymetrix U133 plus 2.0 expression data of 291 CRC cases and 154 controls for discovery of Detector C 2.0. Random forest was used for feature (gene) selection and the support vector machine algorithm was employed as classifier in 600 repetitions of double-nested bootstraps to discriminate between cases and controls. Within each repetition, randomly chosen 23 controls and 160 CRC cases served as prospective validation set. The most frequent chosen genes for discrimination between cases and controls formed the consensus signature, namely Detector C 2.0. Results: Choosing a signature length of 1000 genes resulted in the following second order unbiased prospective performance estimates: S+=0.916 (95% CI 0.863-0.954) and S-= 0.948 (95% CI 0.773-0.994). S+ for UICC stage I and stage II cases were 0.93 and 0.94. S+ for high-grade intraepithelial neoplasia was ∼ 0.67 and S+ for adenoma ≥ 10 mm was ∼ 0.45. Conclusions: Using a three times larger discovery set for Detector C 2.0 than for Detector C we improved S+ (cancer detection rate) by 1.6% to 91.6%. The most important enhancement is the high S- of 94.8% of Detector C 2.0 which is six percent higher than the S- of Detector C. Detector C 2.0 is based on a much larger pts set and should be even more robust than Detector C. We will prospectively validate this test in the largest case-control study ever performed in early detection of CRC.

Prevention, Early Detection, and Overdiagnosis of Colorectal Cancer Within 10 Years of Screening Colonoscopy in Germany

2015 ◽  
Vol 13 (4) ◽  
pp. 717-723 ◽  
Author(s):  
Hermann Brenner ◽  
Lutz Altenhofen ◽  
Christian Stock ◽  
Michael Hoffmeister
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Screening Colonoscopy

scholarly journals Colorectal Cancer after Kidney Transplantation: A Screening Colonoscopy Case-Control Study

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 937
Author(s):  
Francesca Privitera ◽  
Rossella Gioco ◽  
Alba Ilari Civit ◽  
Daniela Corona ◽  
Simone Cremona ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kidney Transplant ◽  
Colorectal Adenomas ◽  
Screening Colonoscopy ◽  
Advanced Adenoma ◽  
Healthy Population ◽  
Transplant Recipients ◽  
Healthy Individuals ◽  
Kidney Transplant Recipients ◽  
Increased Risk

The incidence of colorectal cancer in kidney transplant recipients has been previously reported with conflicting results. In this study, we investigated if the incidence of colorectal advanced neoplasms in kidney transplant recipients, evaluated with screening colonoscopy, was higher than in healthy individuals. One-hundred sixty kidney transplant recipients undergoing screening colonoscopy were compared with 594 age- and sex-matched healthy individuals. Advanced colorectal neoplasia was found in 22 patients (13.7%), including four patients (2.5%) with colorectal cancer. Compared with the healthy population, kidney transplant recipients did not have an increased risk of developing a colorectal cancer (OR 0.69; 95% CI 0.236–2.063, p = 0.688) although it developed at a younger age. In contrast, kidney transplant recipients had a higher risk of developing an advanced adenoma compared with the control group (OR 1.65; 95% CI 0.930–2.981, p = 0.04). In conclusion, kidney transplant recipients did not have an increased incidence of colorectal cancer compared with healthy population. However, transplant patients displayed a higher incidence of colorectal adenomas, suggesting that screening colonoscopy in kidney transplant recipients should be expanded to include even younger recipients (<50 years old).

scholarly journals Invitation of non-attenders to colorectal cancer screening: impact on coverage by examination

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
O Majek ◽  
O Ngo ◽  
B Seifert ◽  
S Suchanek ◽  
M Zavoral ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Early Detection ◽  
Colorectal Cancer Screening ◽  
Colorectal Neoplasia ◽  
Target Population ◽  
Screening Colonoscopy ◽  
Complete Coverage ◽  
Crc Screening ◽  
Incidence And Mortality

Abstract Issue Colorectal cancer (CRC) has been among the most important cancer causes of death globally. CRC screening and early detection can decrease CRC incidence and mortality through timely removal of colorectal neoplasia or early CRC treatment. CRC screening has been initiated in the Czech Republic in 2000 for individuals over 50, with GPs having a key role in recruiting individuals to screening, offering faecal occult blood test (FOBT). Screening colonoscopy (CS) was added for individuals over 55 since 2009. Description of the problem To increase uptake of CRC screening, personal invitation of non-attenders under 70 was implemented in 2014, along with temporary mass-media campaign. Health insurance companies have been sending invitations to those individuals without record of recent FOBT, CS or CRC treatment. The aim of our study was to evaluate impact of this policy on complete coverage by examination over 2013-2018. We defined the complete coverage by examination as the proportion of individuals aged 50-69 undergoing examination with CRC early detection potential (FOBT or CS for any indication) during past 3 years. We used newly established National Registry of Reimbursed Health Services as the source of data. Results Complete coverage of the target population (2.7 million individuals aged 50-69) was 44.8 % in 2013. By 2016, the coverage increased to 54.6%. Therefore, almost 300,000 individuals were newly covered by the relevant examinations. By 2018, the coverage decreased to 51.2%. When we consider only screening FOBT examinations, the coverage was 36.9 % in 2013, 45.2% in 2016, and 42.0% in 2018. Lessons In the health system with accessible CS facilities, the policy of non-attenders' invitation for CRC screening resulted not only in increase in coverage by screening examinations; complete coverage also increased. Unfortunately, the positive effect has been fading out, and further actions to sustain high coverage are therefore warranted. Key messages Invitation of non-attenders to colorectal cancer screening increased complete coverage of the target population by examination. Initial increase was followed by a slow decrease in coverage by examination, underlying the need for other actions to increase participation.

scholarly journals Identification and Validation of Novel Serum Autoantibody Biomarkers for Early Detection of Colorectal Cancer and Advanced Adenoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Hejing Wang ◽  
Bei Zhang ◽  
Xiaojin Li ◽  
Donghu Zhou ◽  
Yanmeng Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Advanced Adenoma ◽  
Serum Autoantibody

scholarly journals Feasibility of Methylated CLIP4 in Stool for Early Detection of Colorectal Cancer: A Training Study in Chinese Population

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Cao ◽  
Guodong Zhao ◽  
Yaping Cao ◽  
Zhiliang Chen ◽  
Xiaoyu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Methylation Level ◽  
Precancerous Lesion ◽  
Area Under The Curve ◽  
Final Analysis ◽  
Advanced Adenoma ◽  
Promoter Regions ◽  
Potential Biomarker ◽  
Significant Difference

BackgroundEarly detection of colorectal cancer (CRC) and precancerous lesion is vitally important for mitigating CRC morbidity and mortality. Aberrant DNA methylations in certain promoter regions have been identified to be closely associated with CRC development and progression, suggesting their potential as diagnostic biomarkers for early detection. In this study, we evaluated the performance of methylated CLIP4 in stool specimens as a potential biomarker for CRC detection.MethodsA total of 321 subjects out of 365 enrolled participants were included in the final analysis, including 154 CRC patients, 23 advanced adenoma (AA) patients, 49 small polyp (SP) patients, and 95 healthy controls. CLIP4 methylation level was examined by qPCR with bisulfite converted DNA purified from approximately 5 g stool specimen.ResultsMethylated CLIP4 test showed high sensitivities of 78.3% (95% CI: 55.8%–91.7%) and 90.3% (95% CI: 84.2%–94.3%) for detecting AA and CRC, respectively, with a specificity of 88.4% (95% CI: 79.8%–93.8%). CLIP4 methylation level discriminated AA and CRC patients from control subjects with area under the curve values of 0.892 (95% CI: 0.795–0.988) and 0.961 (95% CI: 0.938–0.983). Further analysis indicated no significant difference in sensitivities among different ages, genders, stages, locations, sides, tumor sizes and differentiation statuses.ConclusionsMethylated CLIP4 showed a strong potential as a noninvasive biomarker for early CRC detection.

scholarly journals Adenoma to Colorectal Cancer Estimated Transition Rates Stratified by BMI Categories—A Cross-Sectional Analysis of Asymptomatic Individuals from Screening Colonoscopy Program

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 62
Author(s):  
Piotr Spychalski ◽  
Jarek Kobiela ◽  
Paulina Wieszczy ◽  
Marek Bugajski ◽  
Jaroslaw Reguła ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Screening Program ◽  
Screening Colonoscopy ◽  
Advanced Adenoma ◽  
Cross Sectional ◽  
Cross Sectional Analysis ◽  
Colonoscopy Screening ◽  
Advanced Lesion ◽  
Advanced Adenomas ◽  
Sectional Analysis

Most colorectal cancers (CRC) assumedly develop from precursor lesions, i.e., colorectal adenomas (adenoma-carcinoma sequence). Epidemiological and clinical data supporting this hypothesis are limited. Therefore, the aim of the present study is to estimate relative dynamics of colorectal adenoma-carcinoma sequence for groups of screenees stratified by BMI (body mass index) based on prevalence data from Polish Colonoscopy Screening Program (PCSP). We performed a cross-sectional analysis of database records of individuals who entered the national opportunistic colonoscopy screening program for CRC in Poland. We calculated prevalence of adenomas and CRCs adjusted for sex, 5-year age group, family history of CRC, smoking, diabetes and use of aspirin, hormonal therapy and proton-pump inhibitors use. Thereafter we calculated estimated transition rate (eTR) with confidence intervals (CIs) defined as adjusted prevalence of more advanced lesion divided by adjusted prevalence of less advanced lesion. All analyzes were stratified according to the BMI categories: normal (BMI 18.0 to <25.0), overweight (BMI 25.0 to <30.0) and obese (BMI ≥ 30.0). Results are reported in the same respective order. After exclusions we performed analyses on 147 385 individuals. We found that prevalence of non-advanced adenomas is increasing with BMI category (12.19%, 13.81%, 14.70%, respectively; p < 0.001). Prevalence of advanced adenomas was increasing with BMI category (5.20%, 5.77%, 6.61%, respectively; p < 0.001). Early CRCs prevalence was the highest for obese individuals (0.55%) and the lowest for overweight individuals (0.44%) with borderline significance (p = 0.055). For advanced CRC we found that prevalence seems to be inversely related to BMI category, however no statistically significant differences were observed (0.35%, 0.31%, 0.28%; p = 0.274). eTR for non-advanced adenoma to advanced adenoma is higher for obese individuals than for overweight individuals with bordering CIs (42.65% vs. 41.81% vs. 44.95%) eTR for advanced adenoma to early CRC is highest for normal individuals, however CIs are overlapping with remaining BMI categories (9.02% vs. 7.67% vs. 8.39%). eTR for early CRC to advanced CRC is lower for obese individuals in comparison to both normal and overweight individuals with marginally overlapping CIs (73.73% vs. 69.90% vs. 50.54%). Obese individuals are more likely to develop adenomas, advanced adenomas and early CRC but less likely to progress to advanced CRC. Therefore, this study provides new evidence that obesity paradox exists for colorectal cancer.

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