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Neoplasma Vol.68, No.3, p.567–571,2021 |
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Title: A pilot prospective study of plasma cell-free DNA whole-genome sequencing identified chromosome 7p copy number gains as a specific biomarker for early lung cancer detection | ||
Author: Hong-Jie Yu, Xiao-Jun Yu, Jia Tang, Xun Lu, Hai-Tao Ma | ||
Abstract: Chromosome 7 plays an important role in lung tumorigenesis. Chromosome 7 copy number changes might be an early event of lung cancer tumorigenesis. Here we investigate whether chromosome 7p copy number gain is a detectable genetic event with plasma cell-free DNA for early lung cancer detection. Eighteen surgical eligible lung cancer patients and eighteen non-cancer controls were recruited. Peripheral blood was collected before surgery. Cell-free DNA was profiled with low coverage whole-genome sequencing. Chromosome 7 copy number gains were defined as chr7 normalized coverage ≥ 1.0005 and P value < 0.05. Plasma cell-free DNA chr7 copy gains were then compared to pathological examinations on surgical tissues. 83.3% of patients were confirmed as malignancy post-operation, 12 patients with adenocarcinoma and 3 with squamous-carcinoma. The other 16.7% were benign lesions. Cell-free DNA was successfully extracted from pre-surgical plasma samples, with a concentration range from 0.18 to 0.49 ng/µl. Chromosome 7 short arm copy gains were found in 66.7% (10/15) patients, including 66.7% (4/6) T1aN0M0 and 50.0% (1/2) Tis patients, otherwise, chr7p gain was found in 0% (0/3) benign lesions. The specificity was further examined in 18 volunteers who undergoing routine body examinations. Meanwhile, positive carcinoembryonic antigen (CEA) and cytokeratin-19-fragment (CYFRA21-1) were only found in 1/18 (5.7%) and 4/18 (22.2%), respectively. Taking together, Ultrasensitive- Chromosomal Aneuploidy Detector (UCAD) chr7p or UCAD chr7p and tumor biomarker positivity can predict 12/15 (80%, 95% CI: 49.0-94.3%) early lung cancers. Further analyses showed that chr7p copy number gains tend to be enriched in normal EGFR/KRAS patients (Fisher’s test, P value = 0.077). Chromosome 7p copy gains is a useful peripheral blood tumor biomarker from lung cancer detection. |
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Keywords: chromosome 7; biomarker; lung cancer | ||
Published online: 23-Feb-2021 | ||
Year: 2021, Volume: 68, Issue: 3 | Page From: 567, Page To: 571 | |
doi:10.4149/neo_2021_201106N1189 |
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