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• W2947632445 abstract "e13072 Background: Tumor cells keep shedding DNA into blood stream. Here we present a retrospective study to investigate the potential of CIN in plasma cell-free DNA (cfDNA) as a minimal-invasive biomarker for early cancer detection and cancer treatment responses monitoring. Methods: To characterization cfDNA CIN, 160 plasma samples from non-cancer individuals and 569 from cancer patients, including tumors from the brain, respiratory tract, gastrointestinal tract, urinary tract, liver, gallbladder, female reproductive system, prostate, breast and sarcoma. cfDNA was extracted and sent to low-coverage whole genome sequencing by the Illumina X10, followed by CIN analyses by a customized workflow Ultrasensitive Chromosomal Instability Detector (UCAD). Results: In non-cancer individuals, increased CIN in cfDNA was found associated with active EBV infections(P<0.01) and HBV infection (P=0.042). No statistical significances were found for the other parameters, including age, hypertension, diabetes, chronic kidney diseases, family history of cancer and etc. cfDNA CIN increased along with the development of lung cancer lesions, from adenocarcinoma in-situ, minimal invasive adenocarcinoma, invasive adenocarcinoma (P=0.034) to relapsed cancer (P<0.01). The sensitivity of early lung cancer detection was 30.7%, 37.5%, 45.5%, 50.0% and 98.1% for AIS, MIA, IAC, SCC and relapsed lung cancer, at a specificity of 75%. cfDNA CIN levels did not show statistical differences regarding metastases sites. cfDNA CIN were further increased in relapsed breast cancer (P<0.01). The sensitivity of relapsed breast cancer detection was 73.3%, 94.4%, 89.6% and 80.0% for HER2+, Luminal A, Luminal B and triple negative breast cancer, at a specificity of 90%. In primary liver cancer, cfDNA CIN decreased after curative therapies, including R0 resections and liver transplant. R0 resections showed similar performance as compared to liver transplant (P=0.35) in terms of cfDNA CIN decreasing. Furthermore, cfDNA CIN was higher in patients after R0 resections (P=0.003) and liver transplant (P=0.03) than that of HBV-positive cancer-free patients, indicating the potential risk of disease relapses. For advanced stage patients, continuously increasing cfDNA CIN level was found associated with worse survival, and a decreasing trend predicting better prognosis vice versa. Conclusions: Plasma cfDNA CIN analysis might be a useful tool for cancer management." @default.
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• W2947632445 date "2019-05-20" @default.
• W2947632445 modified "2023-09-24" @default.
• W2947632445 title "Development of a plasma cell-free DNA chromosome instabilities assay for early cancer detection and treatment response monitoring of multiple tumor types." @default.
• W2947632445 doi "https://doi.org/10.1200/jco.2019.37.15_suppl.e13072" @default.
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