A Pilot Prospective Study of Plasma Cell free DNA Whole Genome Sequencing Identified Chromosome 7p Copy Number Gains is a Specific Biomarker for Early Lung Cancer detection

purpose: Chromosome 7 is playing an important role in lung tumorigenesis. Here we investigate whether chromosome 7p copy number gain as a detectable genetic events with plasma cell free DNA for early lung cancer detection biomarker. Methods: 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.Results: 83.3% patients were confirmed as malignancy post-operation, with 12 adenocarcinoma and 3 squamous-carcinoma. The other 16.7% were benign lesions. Cell free DNA was successfully extracted from pre-surgical plasma samples, with concentration range from 0.18 to 0.49 ng/ul. 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 CEA and CYFRA21-1 was only found in 1/18 (5.7%) and 4/18 (22.2%). Taking together, 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 tends to be enriched in EGFR/KRAS silent patients (fisher. test, P value=0.077). Conclusions: Chromosome 7p copy gains might be a useful peripheral blood tumor biomarker from lung cancer detection.