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Circulating cell free DNA as the diagnostic marker for colorectal cancer: a systematic review and meta-analysis.

ABSTRACT: Quantitative analyses of circulating cell-free DNA (cfDNA) are suggested to be a promising method for the detection of colorectal cancer, validated clinical relevance of cfDNA has not been published so far. Though some of the inconsistent results were published. This study is the first meta-analysis to systematically evaluate the diagnostic accuracy of circulating cfDNA as non-invasive biomarkers for colorectal cancer.Fourteen studies concerning a quantitative analysis of circulating cfDNA for the diagnosis of colorectal cancer met the inclusion criteria. Data includes 1,258 patients with colorectal cancer and 803 healthy individuals as control was analyzed. The summary estimates were as follow: sensitivity, 0.735 (95% CI 0.713-0.757); specificity, 0.918 (95% CI, 0.900-0.934); positive likelihood ratio, 8.295 (95% CI, 5.037-13.659); negative likelihood ratio, 0.300 (95% CI, 0.231-0.391); diagnostic odds ratio, 30.783 (95% CI, 16.965-55.856); and area under the curve, 0.8818 (95% CI, 0.88-0.93), respectively. Publication bias was not evident with Deeks' funnel plot asymmetry test (p = 0.197).A systematic literature was searched in PubMed, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from their inception to August 07, 2017. Analyses were conducted by Meta-DiSc 1.4 and Stata 12.0. Diagnostic accuracy in sensitivity, specificity and aspects were pooled. Subgroup analyses and meta-regression were performed to identify the sources of heterogeneity. Clinical utility of the cfDNA was evaluated by Fagan nomogram.Our meta-analysis suggested that the diagnostic accuracy of circulating cfDNA has unsatisfactory sensitivity but acceptable specificity for diagnosis of colorectal cancer. Furthermore, the integrity index (ALU247/ALU115) is better than absolute DNA concentration in diagnostic accuracy of colorectal cancer.

SUBMITTER: Wang X

PROVIDER: S-EPMC5966252 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Circulating cell free DNA as the diagnostic marker for colorectal cancer: a systematic review and meta-analysis.

Wang Xin X Shi Xia-Qing XQ Zeng Peng-Wei PW Mo Fong-Ming FM Chen Zi-Hua ZH

Oncotarget 20180511 36

<h4>Background</h4>Quantitative analyses of circulating cell-free DNA (cfDNA) are suggested to be a promising method for the detection of colorectal cancer, validated clinical relevance of cfDNA has not been published so far. Though some of the inconsistent results were published. This study is the first meta-analysis to systematically evaluate the diagnostic accuracy of circulating cfDNA as non-invasive biomarkers for colorectal cancer.<h4>Results</h4>Fourteen studies concerning a quantitative ...[more]

PMID: 29849957

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Project description:BackgroundEarly diagnosis of non-small cell lung cancer (NSCLC) is crucial for treatment. Circulating cell-free DNA (cfDNA) is an extracellular nucleic acid found in serum, and tumor cfDNA circulating in the blood may be used as a biomarker for early diagnosis. The purpose of this study was to evaluate the application value of cfDNA as a biomarker for the diagnosis of NSCLC through meta-analysis.MethodsWe searched the China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science databases using the following search terms: lung cancer, NSCLC, biomarkers, circulating cfDNA, cfDNA, circulating tumor DNA (ctDNA), circulating cell-free tumor DNA, and diagnosis. The retrieval period was set until September 2021. According to PICOS (patients, intervention, comparison, outcomes, and study design) principles the inclusion criteria were: aged ≥18 years; at least 10 NSCLC cases; NSCLC patients diagnosed by histopathology or cytology; circulating cfDNA was detected; outcome data could be completely extracted. Bias risk assessment was conducted according to the QUADAS (Quality Assessment of Diagnostic Accuracy Studies). RevMan 5.3 was used for meta-analysis.ResultsEight studies met the inclusion criteria, including a total of 618 NSCLC patients and 635 healthy subjects. The overall sensitivity and specificity were 0.79 [95% confidence interval (CI): 0.75-0.82] and 0.81 (95% CI: 0.78-0.84), respectively. The area under the curve (AUC) of the summary receiving operating characteristic (SROC) curve was 0.8941. The pooled positive likelihood ratio, pooled negative likelihood ratio, and pooled diagnostic odds ratio were 5.37 (95% CI: 2.67-10.81), 0.24 (95% CI: 0.15-0.38), and 24.68 (95% CI: 8.85-68.84), respectively. The patient selection bias was high in two articles was high, unclear in one article, and low in the remaining five ones. The risk of bias in the research index test was unclear in one article, and low in the remaining seven articles. The reference standard bias, and flow and time bias of all articles was low.ConclusionsCirculating cfDNA is an efficacy biomarker in diagnosis of NSCLC. Its clinical application technology is worthy of further research.

Project description:BackgroundCirculating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor-specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor-specific mutations, whereas the use of total cell-free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta-analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.Materials and methodsA systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed, and meta-analysis applied on both aggregate data extraction and individual patients' data.ResultsTen eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta-analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03-2.82, p < .0001).ConclusionThe total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut-off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor-specific mutations was emphasized in a large individual patients' data meta-analysis.Implications for practiceReliable prognostic markers could help to guide patients and treating physicians regarding the relevance and choice of systemic therapy. Small fragments of circulating cell-free DNA (cfDNA) can be measured in a simple blood sample. This report presents the first meta-analysis of the prognostic value of total cfDNA measurement in patients with metastatic colorectal cancer. Data from 1,076 patients confirmed that patients with the lowest pre-treatment levels of cfDNA had a significantly higher chance of longer survival than those with higher levels. Cell-free DNA analysis can also be used for detection of tumor-specific mutations, and hold potential as a valuable tool in colorectal cancer treatment.

Dataset Information

Circulating cell free DNA as the diagnostic marker for colorectal cancer: a systematic review and meta-analysis.

Publications

Circulating cell free DNA as the diagnostic marker for colorectal cancer: a systematic review and meta-analysis.

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