scholarly journals A Hypothesis-Directed Approach to the Targeted Development of a Multiplexed Proteomic Biomarker Assay for Cancer

2015 ◽  
Vol 14 ◽  
pp. CIN.S24388 ◽  
Author(s):  
Emily M. Mackay ◽  
Jennifer Koppel ◽  
Pooja Das ◽  
Joanna Woo ◽  
David C. Schriemer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Diagnostic Test ◽  
Clinical Setting ◽  
Ranking Method ◽  
Clinical Validation ◽  
Protein Biomarkers ◽  
Clinical Applicability ◽  
Candidate Protein ◽  
Selection Of

In recent years, hundreds of candidate protein biomarkers have been identified using discovery-based proteomics. Despite the large number of candidate biomarkers, few proteins advance to clinical validation. We propose a hypothesis-driven approach to identify candidate biomarkers, previously characterized in the literature, with the highest probability of clinical applicability. A ranking method, called the “hypothesis-directed biomarker ranking” (HDBR) system, was developed to score candidate biomarkers based on seven criteria deemed important in the selection of clinically useful biomarkers. To demonstrate its application, we applied the HDBR system to identify candidate biomarkers for the development of a diagnostic test for the early detection of colorectal cancer. One-hundred and fifty-one candidate biomarkers were identified from the literature and ranked based on the specified criteria. The top-ranked candidates represent a group of biomarkers whose further study and validation would be justified in order to expedite the development of biomarkers that could be used in a clinical setting.

scholarly journals Gel-Based Proteomics of Clinical Samples Identifies Potential Serological Biomarkers for Early Detection of Colorectal Cancer

2019 ◽  
Vol 20 (23) ◽  
pp. 6082 ◽  
Author(s):  
Stine Thorsen ◽  
Irina Gromova ◽  
Ib Christensen ◽  
Simon Fredriksson ◽  
Claus Andersen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Biomarker Discovery ◽  
Real Life ◽  
Clinical Samples ◽  
Plasma Samples ◽  
Healthy Individuals ◽  
Protein Biomarkers ◽  
2D Gel ◽  
Cancer Diseases

The burden of colorectal cancer (CRC) is considerable—approximately 1.8 million people are diagnosed each year with CRC and of these about half will succumb to the disease. In the case of CRC, there is strong evidence that an early diagnosis leads to a better prognosis, with metastatic CRC having a 5-year survival that is only slightly greater than 10% compared with up to 90% for stage I CRC. Clearly, biomarkers for the early detection of CRC would have a major clinical impact. We implemented a coherent gel-based proteomics biomarker discovery platform for the identification of clinically useful biomarkers for the early detection of CRC. Potential protein biomarkers were identified by a 2D gel-based analysis of a cohort composed of 128 CRC and site-matched normal tissue biopsies. Potential biomarkers were prioritized and assays to quantitatively measure plasma expression of the candidate biomarkers were developed. Those biomarkers that fulfilled the preset criteria for technical validity were validated in a case-control set of plasma samples, including 70 patients with CRC, adenomas, or non-cancer diseases and healthy individuals in each group. We identified 63 consistently upregulated polypeptides (factor of four-fold or more) in our proteomics analysis. We selected 10 out of these 63 upregulated polypeptides, and established assays to measure the concentration of each one of the ten biomarkers in plasma samples. Biomarker levels were analyzed in plasma samples from healthy individuals, individuals with adenomas, CRC patients, and patients with non-cancer diseases and we identified one protein, tropomyosin 3 (Tpm3) that could discriminate CRC at a significant level (p = 0.0146). Our results suggest that at least one of the identified proteins, Tpm3, could be used as a biomarker in the early detection of CRC, and further studies should provide unequivocal evidence for the real-life clinical validity and usefulness of Tpm3.

scholarly journals Utility of the methylated SEPT9 test for the early detection of colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy

2020 ◽  
Vol 7 (1) ◽  
pp. e000355 ◽  
Author(s):  
Rohit Hariharan ◽  
Mark Jenkins
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Early Detection ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Diagnostic Test ◽  
Predictive Value ◽  
Meta Analysis ◽  
Test Accuracy ◽  
Sensitivity Specificity

BackgroundCirculating tumour DNA from colorectal cancer (CRC) is a biomarker for early detection of the disease and therefore potentially useful for screening. One such biomarker is the methylated SEPT9 (mSEPT9) gene, which occurs during CRC tumourigenesis. This systematic review and meta-analysis aims to establish the sensitivity, specificity and accuracy of mSEPT9 tests for the early diagnosis of CRC.MethodsA systematic search of the relevant literature was conducted using Medline and Embase databases. Data were extracted from the eligible studies and analysed to estimate pooled sensitivity, specificity and diagnostic test accuracy.ResultsBased on 19 studies, the pooled estimates (and 95% CIs) for mSEPT9 to detect CRC were: sensitivity 69% (62–75); specificity 92% (89–95); positive likelihood ratio 9.1 (6.1–13.8); negative likelihood ratio 0.34 (0.27–0.42); diagnostic OR 27 (15–48) and area under the curve 0.89 (0.86–0.91). The test has a positive predictive value of 2.6% and negative predictive value of 99.9% in an average risk population (0.3% CRC prevalence), and 9.5% (positive predictive value) and 99.6% (negative predictive value) in a high-risk population (1.2% CRC prevalence).ConclusionThe mSEPT9 test has high specificity and moderate sensitivity for CRC and is therefore a potential alternative screening method for those declining faecal immunochemical test for occult blood (FIT) or other screening modalities. However, it is limited by its poor diagnostic performance for precancerous lesions (advanced adenomas and polyps) and its relatively high costs, and little is known about its acceptability to those declining to use the FIT.

scholarly journals Development and Clinical Validation of a Blood Test Based on 29-Gene Expression for Early Detection of Colorectal Cancer

2016 ◽  
Vol 22 (18) ◽  
pp. 4604-4611 ◽  
Author(s):  
Laura Ciarloni ◽  
Sahar Hosseinian Ehrensberger ◽  
Natsuko Imaizumi ◽  
Sylvain Monnier-Benoit ◽  
Cristina Nichita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Early Detection ◽  
Blood Test ◽  
Clinical Validation

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

2015 ◽  
Vol 21 (14) ◽  
pp. 3318-3326 ◽  
Author(s):  
Hongda Chen ◽  
Manuela Zucknick ◽  
Simone Werner ◽  
Phillip Knebel ◽  
Hermann Brenner
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Plasma Protein ◽  
Protein Biomarkers

scholarly journals Multiplex screening of 275 plasma protein biomarkers to identify a signature for early detection of colorectal cancer

2019 ◽  
Vol 14 (1) ◽  
pp. 8-21 ◽  
Author(s):  
Megha Bhardwaj ◽  
Korbinian Weigl ◽  
Kaja Tikk ◽  
Axel Benner ◽  
Petra Schrotz‐King ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Plasma Protein ◽  
Protein Biomarkers

Detector-C: A Blood-based IVD with High Sensitivity and Specificity for Early Detection and Screening of Colorectal Cancer

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
A Rosenthal ◽  
H Köppen ◽  
R Musikowski ◽  
R Schwanitz ◽  
J Behrendt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Sensitivity And Specificity ◽  
High Sensitivity

Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

2020 ◽  
Vol 22 (1) ◽  
pp. 137-145
Author(s):  
Tomasz Mackiewicz ◽  
Aleksander Sowa ◽  
Jakub Fichna
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Cancer Development ◽  
Sporadic Colorectal Cancer ◽  
Future Trends ◽  
Significant Progress ◽  
Current Standard ◽  
Risk Of Cancer ◽  
Histological Testing ◽  
Made In

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

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