Abstract
Background
Cell-free DNA (cfDNA) is emerging as a surrogate sample type for mutation analyses. We investigated the suitability of malignant pleural effusion (MPE) and plasma as a biomaterial for analyzing epidermal growth factor receptor (EGFR) mutation by peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve (PANAMutyper™) analysis.
Methods
Matched tissue, MPE cell block (MPE-CB), MPE supernatant, and plasma samples were collected from patients with advanced lung adenocarcinoma who had a MPE at the time of diagnosis. EGFR mutation was assessed by PANAMutyper™.
Results
Mutation analyses in matched tumor tissues, MPE-CB, MPE supernatant, and/or plasma samples were available for 67 patients. In comparison with tumor tissue and MPE-CB, MPE supernatant exhibited 84.4% sensitivity, 97.1% specificity, 96.4% positive predictive value (PPV), and 87.2% negative predictive value (NPV). In the same comparison, plasma exhibited 70.6% sensitivity, 100.0% specificity, 100.0% PPV, and 73.7% NPV. When sorted by mutation type, MPE supernatant had better sensitivity than plasma for the detection of two major EGFR mutations: 93.8% vs. 75.0% for exon 19 deletion and 73.3% vs. 60.0% for L858R.
Conclusions
In this cohort of patients with MPEs, MPE supernatant demonstrated superior diagnostic performance compared with plasma using a PNA-based real-time PCR method.
Acknowledgments
Biospecimens used in this study were provided by the Chungbuk National University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare, and Family Affairs. All samples derived from the National Biobank of Korea were obtained with informed consent under protocols approved by an institutional review board.
Author contributions: O.J.L. conceived and designed the experiments. Y.H.L. performed the experiments. H.S.H. and K.H.L. analyzed the data. S.M.S. and C.G.W. drafted the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2017R1A2B4010169) and supported by the research grant of Chungbuk National University in 2019, funder id: http://dx.doi.org/10.13039/501100002461.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-1139).
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