Dynamic alterations of plasma cell free DNA in response to chemotherapy in children with neuroblastoma

Su, Yan; Wang, Lijun; Wang, Xisi; Yue, Zhixia; Xing, Tong; Zhao, Wen; Zhao, Qian; Duan, Chao; Han, Yi; Qiu, Lihua; Cheng, Xiaoxing; Liu, Yi; Ma, Xiaoli

doi:10.1002/cam4.2045

Cited by 17 publications

(10 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…cfDNA is thought to originate predominantly from tumor cells and hematopoietic cells [34]. We previously showed that inflammation, transfusion, and therapy with granulocyte-colony stimulating factor are key clinical factors affecting the quantification of cfDNA [35]. To avoid detection of cfDNA from non-tumor cells, blood should not be sampled for tumor cfDNA analysis in these three settings.…”

Section: Discussionmentioning

confidence: 99%

“…We previously demonstrated that plasma cfDNA levels correlated strongly with tumor burden in children with NB [23], and could potentially serve as a more effective biomarker than LDH, which is widely used in the clinic. Furthermore, plasma cfDNA concentrations were significantly lower in patients with PR compared with SD, and the concentrations were dynamically associated with changing tumor burden in response to chemotherapy [35]. However, whether cfDNA could serve as an effective molecular marker for recurrence was unknown.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Wang²,

Jiang

et al. 2020

BMC Cancer

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Wang²,

Jiang

et al. 2020

BMC Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, in recent years, many reports have confirmed the important role of cfDNA in the diagnosis and prognosis of renal cancer, colorectal cancer, neuroblastoma, and pancreatic cancer. [18][19][20][21] Based on the above research results, cfDNA may be a specific, non-invasive and cost-effective new biomarker, which has great potential value for clinical cancer detection. This study performed a quantitative study on the plasma cfDNA concentration changes in patients with advanced GC chemotherapy during chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

<p>Plasma cfDNA as a Potential Biomarker to Evaluate the Efficacy of Chemotherapy in Gastric Cancer</p>

Zhong¹,

Fan²,

Zhou³

et al. 2020

CMAR

View full text Add to dashboard Cite

To investigate the clinical value of plasma cell-free DNA (cfDNA) as a potential biomarker for advanced gastric cancer (GC). Patients and Methods: One hundred and six cases of advanced gastric cancer patients receiving chemotherapy were selected as study objects. Another 40 healthy volunteers were included as control groups. Plasma cfDNA concentration was detected by (SuperbDNA TM) hybridization. Changes in cfDNA concentration during chemotherapy in patients with gastric cancer whose efficacy was assessed as partial response (PR), stable disease (SD) and disease progression (PD) were analyzed respectively. The relationship between the level of cfDNA and the efficacy of chemotherapy and clinical characteristics was also explored. In addition, cfDNA and other tumor markers were subjected to specificity and sensitivity analyses using ROC. Results: cfDNA concentration in advanced GC patients was significantly higher than that in healthy controls (P<0.05). The concentration of plasma cfDNA in patients with PD showed an increasing trend over time. The concentration of plasma cfDNA in patients with therapeutic effect of PR decreased over time. In patients with therapeutic effect of SD, the plasma DNA concentration showed a stable trend over time. There was no significant correlation between cfDNA concentration and factors including gender, age, pathological type, CA724, CA125,CA199, AFP and CEA. ROC results showed that the area under the curve of cfDNA was larger than other tumor markers. Conclusion: Plasma cfDNA concentration was significantly increased in patients with gastric cancer, and its diagnostic efficacy was superior to that of traditional tumor markers. It can be used as a tumor biomarker to monitor the efficacy of chemotherapy for gastric cancer.

show abstract

“…To depict tumor heterogeneity and minimal residual disease, liquid biopsy is recommended to estimate tumor dynamics [24][25][26][27][28]. Recently, plasma cell-free DNA (cfDNA) quantification is emerging as a promising and noninvasive method to predict tumor burden in NB [29][30][31]. More importantly, serum or plasma MYCN copy number quantification by real-time quantitative polymerase chain reaction (qPCR) was used to predict amplified MYCN of tumor in NB, at different cutoff value [32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma

Wang²,

Zhao

et al. 2020

Molecular Oncology

Self Cite

View full text Add to dashboard Cite

Detection of amplification of the MYCN gene is essential for determining optimal treatment and estimating prognosis of patients with neuroblastoma (NB). DNA FISH with neuroblastoma tissues or patient-derived bone marrow cells is the standard clinical practice for the detection of MYCN amplification. As tumor cells may often be unavailable, we developed a method to detect MYCN amplification in the plasma of patients with neuroblastoma. Taking single-copy NAGK DNA as reference, we used real-time quantitative PCR (qPCR) to determine the MYCN/NAGK ratio in the plasma of 115 patients diagnosed with NB. An increased MYCN/NAGK ratio in the plasma was consistent with MYCN amplification as assessed by DNA FISH. The AUC for a MYCN/NAGK ratio equal to 6.965 was 0.943, with 86% sensitivity and 100% specificity. Beyond the threshold of 6.965, the MYCN/NAGK ratio correlated with a heavier tumor burden. Event-free and overall survival of two years were significantly shortened in stage 4 patients with a MYCN/NAGK ratio higher than 6.965. Plasma MYCN/NAGK ratios increased in patients with progressive disease and relapse. Thus, we conclude that the determination of the plasma MYCN/ NAGK ratio by qPCR is a noninvasive and reproducible method to measure MYCN amplification in patients with NB.

show abstract

Dynamic alterations of plasma cell free DNA in response to chemotherapy in children with neuroblastoma

Cited by 17 publications

References 26 publications

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

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

<p>Plasma cfDNA as a Potential Biomarker to Evaluate the Efficacy of Chemotherapy in Gastric Cancer</p>

Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma

Contact Info

Product

Resources

About