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Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis

Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a GTPase that acts as a molecular switch for intracellular signal transduction, promoting cell growth and proliferation. Mutations in the KRAS gene represent important biomarkers for NSCLC targeted therapy. However, detection of KRAS mut...

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Autores principales: Palmieri, Maria, Zulato, Elisabetta, Wahl, Sissel Gyrid Freim, Guibert, Nicolas, Frullanti, Elisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640997/
https://www.ncbi.nlm.nih.gov/pubmed/36386815
http://dx.doi.org/10.3389/fgene.2022.1015161
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author Palmieri, Maria
Zulato, Elisabetta
Wahl, Sissel Gyrid Freim
Guibert, Nicolas
Frullanti, Elisa
author_facet Palmieri, Maria
Zulato, Elisabetta
Wahl, Sissel Gyrid Freim
Guibert, Nicolas
Frullanti, Elisa
author_sort Palmieri, Maria
collection PubMed
description Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a GTPase that acts as a molecular switch for intracellular signal transduction, promoting cell growth and proliferation. Mutations in the KRAS gene represent important biomarkers for NSCLC targeted therapy. However, detection of KRAS mutations in tissues has shown some limitations. During the last years, analyses of circulating free DNA (cfDNA) has emerged as an alternative and minimally invasive, approach to investigate tumor molecular changes. Here, we assessed the diagnostic performance of cfDNA analysis, compared to tissues through a meta-analysis and systematic review of existing literature. From 561 candidate papers, we finally identified 40 studies, including 2,805 NSCLC patients. We extracted values relating to the number of true-positive, false-positive, false-negative, and true-negative. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, each with 95% CI, were calculated. A summary receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the overall diagnostic performance. The pooled sensitivity was 0.71 (95% CI 0.68–0.74) and the specificity was 0.93 (95% CI 0.92–0.94). The diagnostic odds ratio was 35.24 (95% CI 24.88–49.91) and the area under the curve was 0.92 (SE = 0.094). These results provide evidence that detection of KRAS mutation using cfDNA testing is of adequate diagnostic accuracy thus offering to the clinicians a new promising screening test for NSCLC patients.
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spelling pubmed-96409972022-11-15 Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis Palmieri, Maria Zulato, Elisabetta Wahl, Sissel Gyrid Freim Guibert, Nicolas Frullanti, Elisa Front Genet Genetics Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a GTPase that acts as a molecular switch for intracellular signal transduction, promoting cell growth and proliferation. Mutations in the KRAS gene represent important biomarkers for NSCLC targeted therapy. However, detection of KRAS mutations in tissues has shown some limitations. During the last years, analyses of circulating free DNA (cfDNA) has emerged as an alternative and minimally invasive, approach to investigate tumor molecular changes. Here, we assessed the diagnostic performance of cfDNA analysis, compared to tissues through a meta-analysis and systematic review of existing literature. From 561 candidate papers, we finally identified 40 studies, including 2,805 NSCLC patients. We extracted values relating to the number of true-positive, false-positive, false-negative, and true-negative. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, each with 95% CI, were calculated. A summary receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the overall diagnostic performance. The pooled sensitivity was 0.71 (95% CI 0.68–0.74) and the specificity was 0.93 (95% CI 0.92–0.94). The diagnostic odds ratio was 35.24 (95% CI 24.88–49.91) and the area under the curve was 0.92 (SE = 0.094). These results provide evidence that detection of KRAS mutation using cfDNA testing is of adequate diagnostic accuracy thus offering to the clinicians a new promising screening test for NSCLC patients. Frontiers Media S.A. 2022-10-25 /pmc/articles/PMC9640997/ /pubmed/36386815 http://dx.doi.org/10.3389/fgene.2022.1015161 Text en Copyright © 2022 Palmieri, Zulato, Wahl, Guibert and Frullanti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Palmieri, Maria
Zulato, Elisabetta
Wahl, Sissel Gyrid Freim
Guibert, Nicolas
Frullanti, Elisa
Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
title Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
title_full Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
title_fullStr Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
title_full_unstemmed Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
title_short Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
title_sort diagnostic accuracy of circulating free dna testing for the detection of kras mutations in non-small cell lung cancer: a systematic review and meta-analysis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640997/
https://www.ncbi.nlm.nih.gov/pubmed/36386815
http://dx.doi.org/10.3389/fgene.2022.1015161
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