Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis
Background and objective Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | zho |
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Chinese Anti-Cancer Association; Chinese Antituberculosis Association
2018-05-01
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| Series: | Chinese Journal of Lung Cancer |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.3779/j.issn.1009-3419.2018.05.06 |
| _version_ | 1818310503709016064 |
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| author | Fei SU Ke ZHENG Yiyun FU Qian WU Yuan TANG Weiya WANG Lili JIANG |
| author_facet | Fei SU Ke ZHENG Yiyun FU Qian WU Yuan TANG Weiya WANG Lili JIANG |
| author_sort | Fei SU |
| collection | DOAJ |
| description | Background and objective Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. Methods ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. Results The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). Conclusion For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy. |
| first_indexed | 2024-12-13T07:47:06Z |
| format | Article |
| id | doaj.art-e35cbb6ee6f944cdbeba10e0c4c51263 |
| institution | Directory Open Access Journal |
| issn | 1009-3419 1999-6187 |
| language | zho |
| last_indexed | 2024-12-13T07:47:06Z |
| publishDate | 2018-05-01 |
| publisher | Chinese Anti-Cancer Association; Chinese Antituberculosis Association |
| record_format | Article |
| series | Chinese Journal of Lung Cancer |
| spelling | doaj.art-e35cbb6ee6f944cdbeba10e0c4c512632022-12-21T23:54:47ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872018-05-0121538939610.3779/j.issn.1009-3419.2018.05.06Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and PrognosisFei SU0Ke ZHENG1Yiyun FU2Qian WU3Yuan TANG4Weiya WANG5Lili JIANG6Department of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaDepartment of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaDepartment of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaDepartment of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaDepartment of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaDepartment of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaDepartment of Pathology, West China Hospital of Sichuan University, Chengdou 610041, ChinaBackground and objective Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. Methods ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. Results The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). Conclusion For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.http://dx.doi.org/10.3779/j.issn.1009-3419.2018.05.06Lung neoplasmsCirculating cell-free DNAEGFRT790MPrognosis |
| spellingShingle | Fei SU Ke ZHENG Yiyun FU Qian WU Yuan TANG Weiya WANG Lili JIANG Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis Chinese Journal of Lung Cancer Lung neoplasms Circulating cell-free DNA EGFR T790M Prognosis |
| title | Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis |
| title_full | Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis |
| title_fullStr | Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis |
| title_full_unstemmed | Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis |
| title_short | Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis |
| title_sort | influence of different therapies on egfr mutants by circulating cell free dna of lung adenocarcinoma and prognosis |
| topic | Lung neoplasms Circulating cell-free DNA EGFR T790M Prognosis |
| url | http://dx.doi.org/10.3779/j.issn.1009-3419.2018.05.06 |
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