Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA

Muyun Peng, Yuancai Xie, Xiaohua Li, Youhui Qian, Xiaonian Tu, Xumei Yao, Fangsheng Cheng, Feiyue Xu, Deju Kong, Bing He, Chaoyu Liu, Fengjun Cao, Haoxian Yang, Fenglei Yu, Chuanbo Xu, Geng Tian

Research output: Contribution to journalArticle

Abstract

Background Early detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery. Methods The multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white cell count genomic DNA (gDNA) and tumour tissue gDNA of each patient were analysed by ultra-deep sequencing to an average of 35 000× of the coding regions of 65 lung cancer-related genes. Results The cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients are at stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for stages I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harboured mutations in the patients with lung cancer with the largest number found in TP53 (30% plasma and 62% tumour tissue samples) and EGFR (20% and 40%, respectively). Conclusion Plasma ctDNA was analysed in lung nodule assessment and early cancer detection, while an algorithm combining clinical information enhanced the test performance. Trial registration number NCT03081741.

Original languageEnglish (US)
Pages (from-to)647-653
Number of pages7
JournalJournal of medical genetics
Volume56
Issue number10
DOIs
StatePublished - Oct 1 2019

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High-Throughput Nucleotide Sequencing
Plasma Cells
Lung
Mutation
DNA
Lung Neoplasms
Genes
Neoplasms
Early Detection of Cancer
Lung Diseases
Circulating Neoplastic Cells
Neoplasm Genes
Imagery (Psychotherapy)
Discriminant Analysis
Multicenter Studies
Cell Count
Biomarkers
Sensitivity and Specificity

Keywords

  • circulating tumor DNA
  • liquid biopsy
  • lung cancer detection
  • lung nodule malignancy
  • targeted gene NGS sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA. / Peng, Muyun; Xie, Yuancai; Li, Xiaohua; Qian, Youhui; Tu, Xiaonian; Yao, Xumei; Cheng, Fangsheng; Xu, Feiyue; Kong, Deju; He, Bing; Liu, Chaoyu; Cao, Fengjun; Yang, Haoxian; Yu, Fenglei; Xu, Chuanbo; Tian, Geng.

In: Journal of medical genetics, Vol. 56, No. 10, 01.10.2019, p. 647-653.

Research output: Contribution to journalArticle

Peng, M, Xie, Y, Li, X, Qian, Y, Tu, X, Yao, X, Cheng, F, Xu, F, Kong, D, He, B, Liu, C, Cao, F, Yang, H, Yu, F, Xu, C & Tian, G 2019, 'Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA', Journal of medical genetics, vol. 56, no. 10, pp. 647-653. https://doi.org/10.1136/jmedgenet-2018-105825
Peng, Muyun ; Xie, Yuancai ; Li, Xiaohua ; Qian, Youhui ; Tu, Xiaonian ; Yao, Xumei ; Cheng, Fangsheng ; Xu, Feiyue ; Kong, Deju ; He, Bing ; Liu, Chaoyu ; Cao, Fengjun ; Yang, Haoxian ; Yu, Fenglei ; Xu, Chuanbo ; Tian, Geng. / Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA. In: Journal of medical genetics. 2019 ; Vol. 56, No. 10. pp. 647-653.
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abstract = "Background Early detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery. Methods The multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white cell count genomic DNA (gDNA) and tumour tissue gDNA of each patient were analysed by ultra-deep sequencing to an average of 35 000× of the coding regions of 65 lung cancer-related genes. Results The cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64{\%} of the cancer patients are at stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91{\%} and specificity of 88{\%}. When ctDNA assay was used as the test, the sensitivity was 69{\%} and specificity 96{\%}. As for the lung cancer patients, the assay detected 63{\%}, 83{\%}, 94{\%} and 100{\%}, for stages I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80{\%} at a specificity of 99{\%}. 29 out of the 65 genes harboured mutations in the patients with lung cancer with the largest number found in TP53 (30{\%} plasma and 62{\%} tumour tissue samples) and EGFR (20{\%} and 40{\%}, respectively). Conclusion Plasma ctDNA was analysed in lung nodule assessment and early cancer detection, while an algorithm combining clinical information enhanced the test performance. Trial registration number NCT03081741.",
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T1 - Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA

AU - Peng, Muyun

AU - Xie, Yuancai

AU - Li, Xiaohua

AU - Qian, Youhui

AU - Tu, Xiaonian

AU - Yao, Xumei

AU - Cheng, Fangsheng

AU - Xu, Feiyue

AU - Kong, Deju

AU - He, Bing

AU - Liu, Chaoyu

AU - Cao, Fengjun

AU - Yang, Haoxian

AU - Yu, Fenglei

AU - Xu, Chuanbo

AU - Tian, Geng

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Background Early detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery. Methods The multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white cell count genomic DNA (gDNA) and tumour tissue gDNA of each patient were analysed by ultra-deep sequencing to an average of 35 000× of the coding regions of 65 lung cancer-related genes. Results The cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients are at stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for stages I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harboured mutations in the patients with lung cancer with the largest number found in TP53 (30% plasma and 62% tumour tissue samples) and EGFR (20% and 40%, respectively). Conclusion Plasma ctDNA was analysed in lung nodule assessment and early cancer detection, while an algorithm combining clinical information enhanced the test performance. Trial registration number NCT03081741.

AB - Background Early detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery. Methods The multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white cell count genomic DNA (gDNA) and tumour tissue gDNA of each patient were analysed by ultra-deep sequencing to an average of 35 000× of the coding regions of 65 lung cancer-related genes. Results The cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients are at stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for stages I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harboured mutations in the patients with lung cancer with the largest number found in TP53 (30% plasma and 62% tumour tissue samples) and EGFR (20% and 40%, respectively). Conclusion Plasma ctDNA was analysed in lung nodule assessment and early cancer detection, while an algorithm combining clinical information enhanced the test performance. Trial registration number NCT03081741.

KW - circulating tumor DNA

KW - liquid biopsy

KW - lung cancer detection

KW - lung nodule malignancy

KW - targeted gene NGS sequencing

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DO - 10.1136/jmedgenet-2018-105825

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