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Meta-Analysis
. 2019 Mar;8(3):1218-1231.
doi: 10.1002/cam4.1989. Epub 2019 Feb 21.

The diagnostic accuracy of circulating free DNA for the detection of KRAS mutation status in colorectal cancer: A meta-analysis

Affiliations
Meta-Analysis

The diagnostic accuracy of circulating free DNA for the detection of KRAS mutation status in colorectal cancer: A meta-analysis

Wenli Xie et al. Cancer Med. 2019 Mar.

Abstract

KRAS mutations have been reported as a reliable biomarker for epidermal growth factor receptor (EGFR) targeted therapy and are also associated with poor prognosis in colorectal cancer (CRC) patients. However, limitations of detecting KRAS mutations in tissues are obvious. KRAS mutations in the peripheral blood can be detected as an alternative to tissue analysis. The objective of this meta-analysis was to evaluate the diagnostic value of cfDNA (circulating free DNA) compared with tissues and to investigate the prognostic potential of cfDNA KRAS mutations in CRC patients. Searches were performed in PubMed, Embase, and Cochrane Library for published studies. We extracted true-positive (TP), false-positive (FP), false-negative (FN), true-negative (TN) values, survival rate of CRC patients with mutant and wild-type KRAS and calculated pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]. We also generated a summary receiver operating characteristic (SROC) curve to evaluate the overall diagnostic potential. Totally, 31 relevant studies were recruited and used for the meta-analysis on the efficacy of cfDNA testing in detecting KRAS mutations. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.637 (95% CI: 0.607-0.666), 0.943 (95% CI: 0.930-0.954), 10.024 (95% CI: 6.912-14.535), 0.347 (95% CI: 0.269-0.447), and 37.882 (95% CI: 22.473-63.857), respectively. The area under the SROC curve was 0.9392. Together, the results suggest that detecting KRAS mutations in cfDNA has adequate diagnostic efficacy in terms of specificity. There is a promising role for cfDNA in the detection of KRAS mutations in CRC patients. However, prospective studies with larger patient cohorts are still required before definitive conclusions of the prognostic potential of cfDNA KRAS mutations in CRC patients were drawn.

Keywords: KRAS mutation; cfDNA; colorectal cancer; diagnostic; meta-analysis.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Flow diagram summarizing selection of studies for inclusion in the systematic review. *In the study reported by Taly47 and the other study by Xu,29 KRAS status was detected by 2 different methods, and Morgan42 detected KRAS status both in serum and plasma, and the data from 2 assays and 2 samples were analyzed as 2 independent studies. Thus, 31 eligible studies were included in the meta‐analysis
Figure 2
Figure 2
Forest plots of the sensitivity and specificity of circulating free DNA (cfDNA). The pooled sensitivity was 0.637 (95% confidence intervals [95% CIs]: 0.607‐0.666), and the pooled specificity was 0.943 (95% CI: 0.930‐0.954)
Figure 3
Figure 3
Summary Receiver Operating Characteristic (SROC) Curve for circulating free DNA (cfDNA) on detection of KRAS status among colorectal cancer (CRC) patients in all studies. The figure also shows 95% confidence contour and 95% prediction contour
Figure 4
Figure 4
Fagan nomogram presents the clinical utility of circulating free DNA (cfDNA) for the detection of KRAS mutations (A). The likelihood ratio matrix of cfDNA for the detection of KRAS mutation (B)
Figure 5
Figure 5
Assessment of the potential publication bias of the 31 included studies. The P value of Deek's funnel plot was 0.96, suggesting no significant publication bias
Figure 6
Figure 6
Sensitivity analysis of the 31 eligible studies. The results indicated that the pooled results were robust and not influenced by individual studies

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