Abstract
BackgroundPostoperative circulation tumor DNA (ctDNA) is a promising method to predict the risk of recurrence. However, the amount of ctDNA in patients with early NSCLC is too small. Cell damages caused during the intraoperative period leads to a significant increase in cell free DNA (cfDNA). Whether cfDNA content is restored to the preoperative level within a short time after surgery may indicate the degree of surgical trauma. In this study, dynamic changes of cfDNA combined with ctDNA in the perioperative period of NSCLC were used to explore the possibility of them as a biomarker to indicate the risk of recurrence.MethodsNSCLC patients who planned to undergo radical resection were investigated. 10ml of peripheral blood was collected before, during and 7 days after surgery. DNA concentration was measured, and a 23-gene NGS panel was performed to detect gene mutations. All the patients would be followed-up for at least 18 months.ResultsA total of 7 patients were sampled. The amount of cfDNA before surgery was 36.6 ± 14.7ng, and increased to 127.2 ± 52.2ng during surgery. 7 days after surgery, it dropped to 45.23 ± 9.41ng in 3 patients and rose to 173.7 ± 80.80ng in the remaining 4. Only 1 patient was ctDNA positive after surgery, with decreasing cfDNA, and he was the only one that relapsed and died within 18 months.ConclusionThe use of ctDNA to predict the risk of postoperative recurrence of NSCLC is a very valuable method, and it may be more reliable if combined with the dynamic changes of cfDNA. The amounts of cfDNA are raised by the operation, but will be polarized after surgery in 7 days. Postoperative NSCLC patients with positive ctDNA and reduced cfDNA have a higher risk of recurrence.
Highlights
Lung cancer is one of the common malignant tumors, with the highest morbidity and mortality worldwide, 85% of which is nonsmall cell lung cancer (NSCLC) [1]
CfDNA is a fragment of DNA released into the plasma after cell apoptosis by lysis, which carries genome-wide DNA information. circulation tumor DNA (ctDNA) is a part of cell free DNA (cfDNA), which can be derived from primary tumors and metastases, even circulating tumor cells (CTC). ctDNA carries a full set of tumor genetic information and can effectively overcome the issues of the spatial heterogeneity of tumors
Liquid biopsy based on ctDNA has been widely used in the selection of treatment regiments of advanced NSCLC, including the identification of therapeutic drug targets, the detection of immunotherapy biomarkers, like blood tumor mutational burden and blood microsatellite instability [4, 5]. ctDNA can be used for early diagnosis and postoperative recurrence risk prediction in early NSCLC
Summary
Lung cancer is one of the common malignant tumors, with the highest morbidity and mortality worldwide, 85% of which is nonsmall cell lung cancer (NSCLC) [1]. The ctDNA abundance of early NSCLC patients, especially for postoperative patients, is even lower than the detection limit of the conventional NGS detection method, which greatly reduces the detection sensitivity and causes falsenegative results. The use of dynamic change of cfDNA combined with ctDNA as a biomarker might provide us a new approach to predict the risk of early NSCLC postoperative recurrence. The dynamic changes of cfDNA and ctDNA during the perioperative period of NSCLC were investigated to explore the possibility of them as a biomarker to indicate the risk of postoperative recurrence. Postoperative circulation tumor DNA (ctDNA) is a promising method to predict the risk of recurrence. Dynamic changes of cfDNA combined with ctDNA in the perioperative period of NSCLC were used to explore the possibility of them as a biomarker to indicate the risk of recurrence
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