Yonsei Med J.  2018 Mar;59(2):211-218. 10.3349/ymj.2018.59.2.211.

Peptide Nucleic Acid Clamping and Direct Sequencing in the Detection of Oncogenic Alterations in Lung Cancer: Systematic Review and Meta-Analysis

• Song JU
• Lee J

• KMID: 2418783
• DOI: http://doi.org/10.3349/ymj.2018.59.2.211

Abstract

PURPOSE
Molecular testing in non-small cell lung cancer (NSCLC) aids in identifying oncogenic alterations. The aim of this study was to compare the rates of detection of oncogenic alterations and responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) according to EGFR mutation status as determined by peptide nucleic acid (PNA) clamping or direct sequencing (DS).
MATERIALS AND METHODS
We performed a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register. Data from included studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and receiver operating characteristic curves. A meta-regression analysis was conducted to identify potential sources of heterogeneity between selected studies.
RESULTS
We identified 10 studies comprising 924 patients. Oncogenic alterations were detected in 340 of 924 cases (36.8%) with PNA clamping and in 250 of 924 (27.1%) with DS. The pooled sensitivities of PNA clamping and DS were 0.93 [95% confidence interval (CI): 0.90−0.95] and 0.69 (95% CI: 0.64−0.73), respectively. According to meta-regression analysis, none of the covariates were found to be significant sources of heterogeneity. With respect to treatment responses to EGFR-TKIs, there was no significant difference therein between EGFR mutations detected by PNA clamping and DS (53.4% vs. 50.8%; risk ratio, 0.99; 95% CI 0.83−1.19; p=0.874).
CONCLUSION
We demonstrated that PNA clamping has a higher sensitivity than DS for detecting oncogenic alterations in NSCLC. Our findings suggest that PNA clamping is a more useful method for clinical practice.

Keyword

Genetic testing; peptide nucleic acids; epidermal growth factor; lung neoplasms

MeSH Terms

Antineoplastic Agents/therapeutic use
Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics
Constriction
Humans
Lung Neoplasms/*genetics
Molecular Diagnostic Techniques
Mutation
Peptide Nucleic Acids/*genetics
Protein Kinase Inhibitors/*therapeutic use
Receptor Protein-Tyrosine Kinases/*genetics
Receptor, Epidermal Growth Factor/*genetics
Sensitivity and Specificity
Sequence Analysis
Sequence Analysis, DNA
Translocation, Genetic
Antineoplastic Agents
Peptide Nucleic Acids
Protein Kinase Inhibitors
Receptor Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Figure

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  Fig. 1 Flow diagram for identification of eligible studies.

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  Fig. 2 Paired forest plots of the sensitivity and specificity of peptide nucleic acid clamping (A and B) and direct sequencing (C and D) for the detection of oncogenic alterations. CI, confidence interval.

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  Fig. 3 SROC curves for peptide nucleic acid clamping (A) and direct sequencing (B) for the detection of oncogenic alterations. SROC, summary receiver operating characteristic; AUC, area under the curve; SE, standard error.

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  Fig. 4 Pooled results of the response to EGFR-tyrosine kinase inhibitors in EGFR activating mutation-positive non-small cell lung cancer detected by PNA clamping and DS. EGFR, epidermal growth factor receptor; PNA, peptide nucleic acid; DS, direct sequencing; RR, risk ratio; CI, confidence interval.

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