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. 2018 May 11;9(36):24514-24524.
doi: 10.18632/oncotarget.25314.

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

Xin Wang  1 , Xia-Qing Shi  2 , Peng-Wei Zeng  1 , Fong-Ming Mo  2 , Zi-Hua Chen  1
Affiliations

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

Xin Wang et al. Oncotarget. .

Abstract

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.

Keywords: circulating cell free DNA; colorectal cancer; diagnosis; meta-analysis.

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Conflict of interest statement

CONFLICTS OF INTEREST Author Zi-Hua Chen declares that he has no conflicts of interest.

Figures

Figure 1
Figure 1. Flowchart showing selection of studies for inclusion in the meta-analysis
Figure 2
Figure 2. Forest plot of the overall pooled
(A) sensitivity; (B) specificity; (C) PLR;(D) NLR; (E) DOR for quantitative analysis of circulating cell free DNA in the diagnosis of colorectal cancer (F). The SROC curve for quantitative analysis of circulating cell free DNA in the diagnosis of colorectal cancer.
Figure 3
Figure 3. The Fagan nomogram for the assessment of clinical utility on circulating cell free DNA
Figure 4
Figure 4. The Deeks’ funnel plot for the detection of publication bias of the included studies
See this image and copyright information in PMC

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