Non‑invasive detection of EGFR and TP53�mutations through the combination of plasma, urine and sputum in advanced non‑small cell lung cancer

Wu, Zhiyong; Yang, Zhen; Li, Chun‐Sun; Zhao, Wei; Liang, Zhixin; Dai, Yu; Zeng, Jing; Zhu, Qiang; Miao, Kai‐Ling; Cui, Donghua; Chen, Liangan

doi:10.3892/ol.2019.10726

Cited by 15 publications

(24 citation statements)

References 40 publications

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“…Fei et al collected spontaneous sputum in a 1.5 mL container [28]. Wu et al collected approximately 5 mL of spontaneous sputum in a mixed solution with an equal volume of Saccomanno's xative and 0.005% dithiothreitol solution at a 1:1 ratio [29,37]. We collected spontaneous sputum using the YM…”

Section: Discussionmentioning

confidence: 99%

Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum using Droplet Digital PCR

Isaka

Yokose

Ito

et al. 2021

Preprint

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Background】It is still unclear whether epidermal growth factor receptor (EGFR) mutation of primary lung adenocarcinoma can be detected accurately on sputum samples. This study aimed to examine EGFR mutations of primary lung adenocarcinoma in sputum samples using droplet digital polymerase chain reaction (ddPCR) and compare it with an EGFR mutation in surgically resected lung cancer. 【Methods】Sputum was collected preoperatively from patients with primary lung cancer who were scheduled for complete resection of lung tumor at Kanagawa Cancer Center from September 2014 to May 2016. ddPCR was performed to detect EGFR exon 21 L858R point mutation (Ex21 mutation) and EGFR exon 19 deletion mutation (Ex19 mutation) in the sputum samples. The concordance of EGFR mutation status in sputum samples and tumors in surgically resected specimen was evaluated for each positive and negative cytology group.【Results】One hundred and eighteen patients with primary lung adenocarcinoma provided sputum samples. Sputum cytology was positive in 13 patients (11.0%). ddPCR detected two cases of Ex21 mutation and two cases of Ex19 mutation. Compared to surgically resected specimens, the sensitivity, specificity, and positive predictive value of EGFR mutation detection were 80.0%, 100%, and 92.3%, respectively. The sensitivity of EGFR mutation detection was 3.1% in sputum cytology negative cases. Logistic regression model analysis revealed that tumor size ≥ 29 mm determined using computed tomography (CT) was an independent potential predictive factor for positive sputum cytology (odds ratio = 10.6, 95% confidence interval: 1.85–61.0, p=0.008).【Conclusions】EGFR mutation of primary lung adenocarcinoma was accurately detected in sputum samples using ddPCR if the sputum cytology was positive. Sputum samples should be collected in patients with CT tumor size ≥ 29 mm for EGFR mutation analysis.

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Section: Discussionmentioning

confidence: 99%

Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum using Droplet Digital PCR

Isaka

Yokose

Ito

et al. 2021

Preprint

View full text Add to dashboard Cite

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Section: Discussionmentioning

confidence: 99%

“…Su, et al performed ampli cation refractory mutation system (ARMS)-PCR for 35 sputum samples containing tumor cells collected from stage III-IV lung cancer patients and reported a 90.9% sensitivity [28]. Wu et al reported a 63% sensitivity when an EGFR sensitizing mutation was analyzed in 50 sputum samples using next-generation sequencing [29]. Presently, ddPCR analysis of 80 sputum samples revealed an 80.0% detection sensitivity for EGFR mutations if the sputum cytology was positive.…”

Section: Discussionmentioning

confidence: 99%

Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum Using Droplet Digital PCR

Isaka

Yokose

Ito

et al. 2020

Preprint

View full text Add to dashboard Cite

Background It is still unclear whether epidermal growth factor receptor (EGFR) mutation of primary lung adenocarcinoma can be detected accurately on sputum samples. This study aimed to examine EGFR mutations of primary lung adenocarcinoma in sputum samples using droplet digital polymerase chain reaction (ddPCR) and compare it with an EGFR mutation in surgically resected lung cancer. Methods Sputum was collected preoperatively from patients with primary lung cancer who were scheduled for complete resection of lung tumor at Kanagawa Cancer Center from September 2014 to May 2016. ddPCR was performed to detect EGFR exon 21 L858R point mutation (Ex21 mutation) and EGFR exon 19 deletion mutation (Ex19 mutation) in the sputum samples. The concordance of EGFR mutation status in sputum samples and tumors in surgically resected specimen was evaluated for each positive and negative cytology group.Results One hundred and eighteen patients with primary lung adenocarcinoma provided sputum samples. Sputum cytology was positive in 13 patients (11.0%). ddPCR detected two cases of Ex21 mutation and two cases of Ex19 mutation. Compared to surgically resected specimens, the sensitivity, specificity, and positive predictive value of EGFR mutation detection were 80.0%, 100%, and 92.3%, respectively. The sensitivity of EGFR mutation detection was 3.1% in sputum cytology negative cases. Logistic regression model analysis revealed that tumor size ≥ 29 mm determined using computed tomography (CT) was an independent potential predictive factor for positive sputum cytology (odds ratio = 10.6, 95% confidence interval: 1.85–61.0, p=0.008).Conclusions EGFR mutation of primary lung adenocarcinoma was accurately detected in sputum samples using ddPCR if the sputum cytology was positive. Sputum samples should be collected in patients with CT tumor size ≥ 29 mm for EGFR mutation analysis.

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“…In addition, both plasma and urine ctDNA could be utilized as markers of colorectal cancer progression [ 160 ]. Similarly, the detection of EGFR and TP53 mutations through the combination of plasma, urine, and sputum could improve the predictive value of personalized treatment of advanced NSCLC [ 161 ]. However, sensitive and accurate methods allowing high depth of sequencing and minimization of artifacts are required for the molecular detection of mutations in urinary DNA.…”

Section: Other Liquid Biopsy Typesmentioning

confidence: 99%

Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management

Líšková

Samec

Koklesová

et al. 2020

JCM

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One in every four deaths is due to cancer in Europe. In view of its increasing incidence, cancer became the leading cause of death and disease burden in Denmark, France, the Netherlands, and the UK. Without essential improvements in cancer prevention, an additional 775,000 cases of annual incidence have been prognosed until 2040. Between 1995 and 2018, the direct costs of cancer doubled from EUR 52 billion to EUR 103 billion in Europe, and per capita health spending on cancer increased by 86% from EUR 105 to EUR 195 in general, whereby Austria, Germany, Switzerland, Benelux, and France spend the most on cancer care compared to other European countries. In view of the consequent severe socio-economic burden on society, the paradigm change from a reactive to a predictive, preventive, and personalized medical approach in the overall cancer management is essential. Concepts of predictive, preventive, and personalized medicine (3PM) demonstrate a great potential to revise the above presented trends and to implement cost-effective healthcare that benefits the patient and society as a whole. At any stage, application of early and predictive diagnostics, targeted prevention, and personalization of medical services are basic pillars making 3PM particularly attractive for the patients as well as ethical and cost-effective healthcare. Optimal 3PM approach requires novel instruments such as well-designed liquid biopsy application. This review article highlights current achievements and details liquid biopsy approaches specifically in cancer management. 3PM-relevant expert recommendations are provided.

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Non‑invasive detection of EGFR and TP53�mutations through the combination of plasma, urine and sputum in advanced non‑small cell lung cancer

Cited by 15 publications

References 40 publications

Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum using Droplet Digital PCR

Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum using Droplet Digital PCR

Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum Using Droplet Digital PCR

Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management

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