scholarly journals Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

2020 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  

Abstract Background: Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence. Methods: A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children’s Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence. Results: Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6% and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL. Conclusions: High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

2020 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  

Abstract Background: Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence. Methods: A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children’s Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence. Results: Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6% and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL. Conclusions: High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.


2019 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  

Abstract Background Neuroblastoma is the third-most common cancer in children. The high rate of tumor recurrence accounts for a low survival rate in high risk neuroblastoma. Therefore it is clinically of extreme importance to find an effective biomarker for alerting disease recurrence.Methods Total 116 high risk neuroblastoma patients were recruited in Beijing Children’s Hospital from February, 2015 to December, 2017. All patients had received multiple-disciplinary treatment, then went into maintenance treatment phase after evaluation. Blood samples were collected to quantify plasma cell-free DNA (cfDNA) at time points of the beginning of maintenance treatment, every three months afterwards, and diagnosis of recurrence.Results Results showed that 36 high risk neuroblastoma patients developed recurrence during maintenance treatment. The plasma cfDNA concentration was significantly higher in recurrence than in event-free patients (29.34 ng/ml VS 10.32 ng/ml). The time span of cfDNA level higher than 29 ng/ml was consistently detected ahead of recurrence at mean of 0.55 months. The ROC analysis showed that AUC was 0.825, optimal sensitivity and specificity of 80.6% and 71.3% respectively, at cfDNA level of 12.93 ng/ml.Conclusions We concluded that high level of plasma cfDNA could serve as a promising molecular marker to alert recurrence disease in high risk neuroblastoma children.


2020 ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  

Abstract Background Neuroblastoma is the third-most common cancer in children. The high rate of tumor recurrence accounts for a low survival rate in high risk neuroblastoma. Therefore it is clinically of extreme importance to find an effective biomarker for alerting disease recurrence.Methods Total 116 high risk neuroblastoma patients were recruited in Beijing Children's Hospital from February, 2015 to December, 2017. All patients had received multiple-disciplinary treatment, then went into maintenance treatment phase after evaluation. Blood samples were collected to quantify plasma cell-free DNA (cfDNA) at time points of the beginning of maintenance treatment, every three months afterwards, and diagnosis of recurrence.Results Results showed that 36 high risk neuroblastoma patients developed recurrence during maintenance treatment. The plasma cfDNA concentration was significantly higher in recurrence than in event-free patients (29.34 ng/ml VS 10.32 ng/ml). The time span of cfDNA level higher than 29 ng/ml was consistently detected ahead of recurrence at mean of 0.55 months. The ROC analysis showed that AUC was 0.825, optimal sensitivity and specificity of 80.6% and 71.3% respectively, at cfDNA level of 12.93 ng/ml.Conclusions We concluded that high level of plasma cfDNA could serve as a promising molecular marker to alert recurrence disease in high risk neuroblastoma children.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Su ◽  
Lijun Wang ◽  
Chiyi Jiang ◽  
Zhixia Yue ◽  
Hongjun Fan ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Valentina Casadio ◽  
Daniele Calistri ◽  
Samanta Salvi ◽  
Roberta Gunelli ◽  
Elisa Carretta ◽  
...  

Circulating cell-free DNA has been recognized as an accurate marker for the diagnosis of prostate cancer, whereas the role of urine cell-free DNA (UCF DNA) has never been evaluated in this setting. It is known that normal apoptotic cells produce highly fragmented DNA while cancer cells release longer DNA. We thus verified the potential role of UCF DNA integrity for early prostate cancer diagnosis. UCF DNA was isolated from 29 prostate cancer patients and 25 healthy volunteers. Sequences longer than 250 bp (c-Myc,BCAS1, andHER2) were quantified by real-time PCR to verify UCF DNA integrity. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 0.7959 (95% CI 0.6729–0.9188). At the best cut-off value of 0.04 ng/μL, UCF DNA integrity analysis showed a sensitivity of 0.79 (95% CI 0.62–0.90) and a specificity of 0.84 (95% CI 0.65–0.94). These preliminary findings indicate that UCF DNA integrity could be a promising noninvasive marker for the early diagnosis of prostate cancer and pave the way for further research into this area.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.


2019 ◽  
Vol 35 (4) ◽  
pp. 714-721 ◽  
Author(s):  
Els M Gielis ◽  
Kristien J Ledeganck ◽  
Amélie Dendooven ◽  
Pieter Meysman ◽  
Charlie Beirnaert ◽  
...  

Abstract Background After transplantation, cell-free deoxyribonucleic acid (DNA) derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to investigate the role of plasma ddcfDNA as biomarker for acute kidney rejection. Methods From 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (Day 1 to 3 months) within a multicentre set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex polymerase chain reaction-based method for the analysis of single nucleotide polymorphisms. Results Increases of the ddcfDNA% above a threshold value of 0.88% were significantly associated with the occurrence of episodes of acute rejection (P = 0.017), acute tubular necrosis (P = 0.011) and acute pyelonephritis (P = 0.032). A receiver operating characteristic curve analysis revealed an equal area under the curve of the ddcfDNA% and serum creatinine of 0.64 for the diagnosis of acute rejection. Conclusions Although increases in plasma ddcfDNA% are associated with graft injury, plasma ddcfDNA does not outperform the diagnostic capacity of the serum creatinine in the diagnosis of acute rejection.


2018 ◽  
Vol 18 (3) ◽  
pp. 421-431 ◽  
Author(s):  
Agnès Marchio ◽  
Marie Amougou Atsama ◽  
Aubin Béré ◽  
Narcisse-Patrice Komas ◽  
Dominique Noah Noah ◽  
...  

Author(s):  
Ashley N. Battarbee ◽  
Neeta L. Vora

In a prospective, multicenter blinded study at 35 international centers, the Noninvasive Examination of Trisomy (NEXT) study evaluated the performance of cell-free DNA screening for fetal trisomy compared to standard first trimester screening with nuchal translucency and serum analytes in a routine prenatal population. Among the 15,841 women who had standard screening and cell-free DNA analysis with neonatal outcome data, there were 68 chromosomal abnormalities (1 in 236). Of these, 38 were Trisomy 21 (1 in 417). Cell-free DNA analysis had a higher area under the curve (AUC) for trisomy 21, compared to standard screening (0.999 vs. 0.958, p = 0.001). Cell-free DNA analysis also had greater sensitivity, specificity, and positive predictive value compared to standard screening for trisomy 21, 18, and 13. While cell-free DNA analysis cannot detect all chromosome abnormalities, it performed better than standard screening for detection of trisomies 21, 18, and 13 in a routine population including low- and high-risk women.


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