Urinary measurement of circulating tumor DNA for treatment monitoring and prognosis of metastatic colorectal cancer patients
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Tao Song
Abstract
Background
Solid tumor tissue testing is the gold standard for molecular-based assays for metastatic colorectal cancer (mCRC). This poses challenges during treatment monitoring. Total DNA derived from urine specimens offers clear advantages to track the disease dynamics. Our study aims to evaluate the sensitivity for total DNA recovered from urine and its clinical relevance to mCRC.
Methods
KRAS mutations in urine specimens were examined in 150 mCRC patients. Baseline concordance was established to determined clinical relevance. The total DNA quantities were also prospectively examined in serial samplings during treatment.
Results
Analysis of the genetic mutations showed good agreement for baseline samples. Matched tumor and urine specimens’ molecular profiles were observed to have 90% concordance. Comparing with healthy volunteers, we established a cutoff of 8.15 ng that demonstrated elevated total DNA levels was associated with mCRC patients (sensitivity: 90.7%; specificity: 82.0%). For patients treated with chemotherapy or anti-epidermal growth factor receptor inhibitors, DNA quantity mirrored early treatment response. Survival analysis showed that patients with sustained elevated quantities of KRAS mutations had poorer outcome.
Conclusions
Total urine DNA offers a viable complement for mutation profiling in mCRC patients, given the good agreement with matched tumor samples. Our study also established that this is specific based on the results from healthy individuals. Serial monitoring of total DNA levels allowed early prediction to treatment response and was effective to identify high risk patients. This is potentially useful to complement current disease management.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by a research grant provided by Xiangyang No. 1 People’s Hospital.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0675).
©2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Obituary
- Jillian Russyll (AKA Jill) Tate
- Editorial
- The long way to standardization of practices: HbA1c as archetypal example
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- Secretory tumors of the pituitary gland: a clinical biochemistry perspective
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- Patient’s knowledge and awareness about the effect of the over-the-counter (OTC) drugs and dietary supplements on laboratory test results: a survey in 18 European countries
- National surveys on 15 quality indicators for the total testing process in clinical laboratories of China from 2015 to 2017
- Urinary albumin strip assay as a screening test to replace quantitative technology in certain conditions
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Artikel in diesem Heft
- Frontmatter
- Obituary
- Jillian Russyll (AKA Jill) Tate
- Editorial
- The long way to standardization of practices: HbA1c as archetypal example
- Reviews
- Secretory tumors of the pituitary gland: a clinical biochemistry perspective
- Thalassemia in the laboratory: pearls, pitfalls, and promises
- Opinion Paper
- Diagnostic biomarkers of muscle injury and exertional rhabdomyolysis
- General Clinical Chemistry and Laboratory Medicine
- Patient’s knowledge and awareness about the effect of the over-the-counter (OTC) drugs and dietary supplements on laboratory test results: a survey in 18 European countries
- National surveys on 15 quality indicators for the total testing process in clinical laboratories of China from 2015 to 2017
- Urinary albumin strip assay as a screening test to replace quantitative technology in certain conditions
- Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis
- Different immunoreactivity of monomers and dimers makes automated free light chains assays not equivalent
- The utility of saliva testing in the estimation of uremic toxin levels in serum
- Determination of cannabinoids in oral fluid and urine of “light cannabis” consumers: a pilot study
- Moving from the second to the third generation Roche PTH assays: what are the consequences for clinical practice?
- Baseline hepcidin measurement in the differential diagnosis of anaemia for elderly patients and its correlation with the increment of transferrin saturation following an oral iron absorption test
- Reference Values and Biological Variations
- A multicenter study for the evaluation of the reference interval for TSH in Italy (ELAS TSH Italian Study)
- Cancer Diagnostics
- Urinary measurement of circulating tumor DNA for treatment monitoring and prognosis of metastatic colorectal cancer patients
- BCL2L12: a multiply spliced gene with independent prognostic significance in breast cancer
- Diabetes
- The global impact of the International Federation of Clinical Chemistry and Laboratory Medicine, Education and Management Division: engaging stakeholders and assessing HbA1c quality in a multicentre study across China
- The frequency of testing for glycated haemoglobin, HbA1c, is linked to the probability of achieving target levels in patients with suboptimally controlled diabetes mellitus
- Letters to the Editor
- Response to article by Caponi et al. about serum free light chains
- Response to Letter to the Editor about immunochemical measurement of urine free light chains
- Estimated GFR-specific 99th percentiles for high-sensitive cardiac troponin T based on the adjusted analytical change limit (adjACL) in hospitalized patients
- Perioperative heart-type fatty acid binding protein concentration cutoffs for the identification of severe acute kidney injury in patients undergoing cardiac surgery
- A peculiar reaction curve with dual spikes in absorbance during a total bilirubin assay in spite of accurate results induced by high M-protein concentration
- Extremely low high-density-lipoprotein cholesterol due to an unusual non-inherited cause: a case report
- A single-center performance evaluation of the fully automated iFlash anti-Müllerian hormone immunoassay
- Genetic polymorphisms and variants in the LDL receptor associated with familial hypercholesterolemia: cascade screening and identification of the variants 666C>A, 862G>A, 901G>A, and 919G>A of a Brazilian family
- Undetected paraganglioma by functional imaging techniques: case report
- A particular case of AML patient with the polymorphism G105G (rs11554137) and the missense mutation R132C in IDH1 gene
- Atypical “hairy cell-like” presentation of leukemic mantle cell lymphoma
- Evaluation of a rapid centrifugation step (4500 g for 2 min) in coagulation assays to monitor direct oral anticoagulants
