Reliability of digital PCR in detecting KRAS mutation in colorectal cancer using plasma sample: A systematic review and meta-analysis

BACKGROUND: Test on the KRAS somatic mutation status is necessary before cetuximab and panitumumab treatments are given to colorectal cancer patients. Metastatic colorectal cancer patients sometimes lack tumor tissue samples, and the testing of KRAS mutation in plasma samples requires highly sensitive methods. OBJECTIVES: The aim of this study was to evaluate the accuracy of digital PCR in detecting KRAS mutation in plasma samples of colorectal cancer patients. DATA SOURCES: Literature research was conducted in Pubmed, Embase, and Cochrane Library. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Database searching found 188 relevant studies. After removing duplicates, eligible studies were selected from 151 publications using the following exclusion criteria: 1. did not discuss colorectal cancer; 2. did not use digital PCR method; 3. lacked plasma sample or tissue sample; 4. did not measure KRAS status; 5. un-interpretable data. STUDY APPRAISAL AND SYNTHESIS METHODS: Data were extracted from the eligible studies by 2 independent researchers. Pooled accuracy parameters were calculated from those extracted data using Meta-DiSc and STATA software. RESULTS: Twelve eligible studies were selected for the systematic review and meta-analysis. After calculation, the pooled sensitivity and specificity were 0.83 (95% CI: 0.79–0.86) and 0.91 (95%CI: 0.88–0.93), respectively. Pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 7.30 (95%CI: 4.78–11.17), 0.22 (95%CI: 0.15–0.32), and 41.00 (95%CI: 21.07–79.78), respectively. Area under curve of the summarized ROC curve was 0.9322. LIMITATIONS: Although no significant bias was identified, number of included studies was still quite small, especially in subgroup analysis. CONCLUSIONS AND IMPLICATION OF KEY FINDINGS: Digital PCR showed high accuracy and could be a reliable detection method for KRAS mutation in plasma samples. Large-cohort prospective study is required to further confirm the usefulness of digital PCR in KRAS mutation detection.