Abstract
BackgroundQuantitative 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.ResultsFourteen 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).Materials and MethodsA 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.ConclusionsOur 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.
Highlights
Colorectal cancer is the third most common cancer worldwide, with 945,000 new cases diagnosed and 492,000 deaths each year
Our meta-analysis suggested that the diagnostic accuracy of circulating cell-free DNA (cfDNA) has unsatisfactory sensitivity but acceptable specificity for diagnosis of colorectal cancer
Fourteen studies [7–20] concerning a quantitative analysis of circulating cfDNA for the diagnosis of colorectal cancer that met the inclusion criteria were identified from 407 publications, including a total of 1,258 patients with colorectal cancer and 803 healthy control individuals
Summary
Colorectal cancer is the third most common cancer worldwide, with 945,000 new cases diagnosed and 492,000 deaths each year. This cancer has vague or nonspecific symptoms, so it is generally diagnosed in the advanced stage. Methods to improve www.oncotarget.com early detection of colorectal cancer in specificity and sensitivity are a critical need. The major available strategies for diagnosis of colorectal cancer include colonoscopy and fecal occult blood testing. Fecal occult blood testing, even colonoscopy, may fail to detect carcinomas at early stage. 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. This study is the first meta-analysis to systematically evaluate the diagnostic accuracy of circulating cfDNA as non-invasive biomarkers for colorectal cancer
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