Increased level and fragmentation of plasma circulating cell-free DNA are diagnostic and prognostic markers for renal cell carcinoma
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Yoshiyuki Yamamoto1, Motohide Uemura1,2, Kosuke Nakano1, Yujiro Hayashi1, Cong Wang1, Yu Ishizuya1, Toshiro Kinouchi1, Takuji Hayashi1, Kyosuke Matsuzaki1, Kentaro Jingushi2, Taigo Kato1, Atsunari Kawashima1, Takeshi Ujike1, Akira Nagahara1, Kazutoshi Fujita1, Ryoichi Imamura1 and Norio Nonomura1
1Department of Urology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
2Department of Therapeutic Urologic Oncology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
Motohide Uemura, email: firstname.lastname@example.org
Keywords: circulating cell-free DNA; renal cell carcinoma; plasma; level; fragment size
Received: December 14, 2017 Accepted: March 11, 2018 Published: April 17, 2018
Background: Reliable biomarkers for renal cell carcinoma (RCC) have yet to be found. Circulating cell-free DNA (cfDNA) is an emerging resource for the diagnosis and prognosis of various cancers. This study aims to identify novel blood biomarkers for RCC.
Materials And Methods: Plasma cfDNA was extracted from RCC patients (n = 92) and healthy controls (n = 41). Levels of cfDNA were determined using quantitative real-time PCR of ACTB as the target gene, and cfDNA fragment size was measured using a microfluidics-based platform. Diagnostic potential was assessed using receiver operating characteristic (ROC) and logistic regression analysis, and prognostic potential was evaluated using log-rank test.
Results: Median levels of cfDNA from RCC patients were significantly higher than those from healthy controls (3803 vs 2242 copies/ml, p < 0.001). Median fragment sizes of cfDNA in RCC patients were shorter than those in healthy controls (170 vs 171 bp, p = 0.052). To evaluate level of cfDNA as a diagnostic tool for RCC, ROC curve analysis revealed a sensitivity of 63.0% and a specificity of 78.1%. Multivariate analysis indicated that age, gender and the level of cfDNA were significantly associated with the presence of RCC (p < 0.001, p = 0.013, p < 0.001, respectively). Additionally, shorter cfDNA fragment size was negatively associated with progression-free survival (p = 0.006).
Conclusions: Our study demonstrates the diagnostic and prognostic potential of plasma cfDNA as a biomarker for RCC.
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