Circulating cell free DNA as the diagnostic marker for colorectal cancer: a systematic review and meta-analysis
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Xin Wang1, Xia-Qing Shi2, Peng-Wei Zeng3, Fong-Ming Mo4 and Zi-Hua Chen5
1Department of General Surgery, Xiangya Hospital of Central South University, Changsha, China
2Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital of Central South University, Changsha, China
3Department of General Surgery, Xiangya Hospital of Central South University, Changsha, China
4Key Laboratory of Nanobiological Technology of Chinese Ministry of Health, Xiangya Hospital of Central South University, Changsha, China
5Department of General Surgery, Xiangya Hospital of Central South University, Changsha, China
Zi-Hua Chen, email: [email protected]
Keywords: circulating cell free DNA; colorectal cancer; diagnosis; meta-analysis
Received: April 27, 2017 Accepted: October 28, 2017 Published: May 11, 2018
Background: 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.
Results: 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).
Materials and Methods: 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.
Conclusions: 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.
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