Plasma cell-free DNA levels and integrity in patients with chest radiological findings: NSCLC versus benign lung nodules

Szpechcinski, Adam; Rudziński, Piotr; Kupis, Włodzimierz; Langfort, Renata; Orłowski, T; Chorostowska‐Wynimko, Joanna

doi:10.1016/j.canlet.2016.02.002

Cited by 39 publications

(30 citation statements)

References 36 publications

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“…15 In addition, it was not only confirmed that the concentration of cfDNA in plasma was higher in NSCLC patients compared to benign lung tumors and healthy controls, but also demonstrated that cfDNA integrity obtained from Ct values of 100-bp qPCR products divided by ones in 400-bp, showed great power (91% sensitivity, 68.2% specificity) to discriminate NSCLC and benign lung tumors. 16 It was shown that mutations in ctDNA only has 50% sensitivity of early detection for lung cancer due to the fewer detectable amounts of ctDNA released by early-stage tumors, while proteins in plasma have also been described to be useful to detect and diagnose lung cancer at early stages. Therefore, an evaluation of a combination of 16 driver genes mutation in ctDNA and eight circulating proteins, including carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), hepatocyte growth factor (HGF), tissue inhibitor of metalloproteinases 1 (TIMP-1) protein levels, pro-lactin (PRL), osteopontin (OPN), and myeloperoxidase (MPO), called CancerSEEK, was conducted to improve the early detection for multiple cancers, including lung cancer.…”

Section: Early Diagnosis Of Lung Cancer By Liquid Biopsymentioning

confidence: 99%

“…An analysis from the trial of CheckMate-026 determined a relationship between high tissue-based TMB and better clinical benefit with nivolumab in NSCLC in the firstline. 9 Aaron et al 8 also provided evidence to show that high TMB (≥20 mutations/mb) predicted better outcomes, including ORR (46% vs 14%; P=0.0025), PFS (10 vs 2.2 months; P=0.0005), and OS(11.1 months vs not reached, P=0.0557) in comparison with low (1-5 mutations/mb) to intermediate (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) mutations/mb) TMB after receiving treatment with anti-PD1/PD-L1 monotherapy. However, obtaining the tumor tissue needed for mutations detection is always a challenge facing the advanced NSCLC patients.…”

Section: Evaluation For Immunotherapy Via Liquid Biopsymentioning

confidence: 99%

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<p>Update on liquid biopsy in clinical management of non-small cell lung cancer</p>

Wu¹,

Yang²,

Dai³

et al. 2019

OTT

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Lung cancer, a leading cause of cancer-related mortality, has a low rate of early diagnosis and a poor prognosis for advanced stages. Recent advances in further mastery of the biology of tumors promote the diagnosis and therapy, especially for non-small cell lung cancer (NSCLC). However, tumor tissue-based information is often not available in most cases due to the invasive and high risk nature of the tumor biopsy procedures. Liquid biopsy, based on the multiple liquid samples including circulating tumor cells (CTC), circulating tumor DNA (ctDNA), and tumor-derived exosome obtained from blood or urine as well as other body fluids, can also provide valuable tumor-related information, playing an important role in management of NSCLC in clinical practice. It is widely believed that concordance of detection for tumor by liquid samples in comparison with tissue biopsy for both early and advanced stage NSCLC patients is optimistic. We herein review the current and future clinical application of liquid biopsy, including early diagnosis and management of precise personalized treatment in lung cancer. The future directions of development for liquid biopsy are also discussed in this review.

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Section: Early Diagnosis Of Lung Cancer By Liquid Biopsymentioning

confidence: 99%

Section: Evaluation For Immunotherapy Via Liquid Biopsymentioning

confidence: 99%

<p>Update on liquid biopsy in clinical management of non-small cell lung cancer</p>

Wu¹,

Yang²,

Dai³

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…It has been experimentally evidenced that tumor cells can release genomic DNA into the blood and circulating DNA can reflect the tumor burden and tumor biologic characteristics [6, 8]. A series of studies have shown that NSCLC patients have higher levels of cfDNA in the blood compared with healthy controls or patients with benign diseases [9–11]. The quantitative assay of cfDNA may be a screening tool for NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Circulating cell-free DNA as a prognostic and predictive biomarker in non-small cell lung cancer

Liu

Huang

et al. 2016

Oncotarget

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Circulating cell-free DNA (cfDNA), which can be obtained from plasma or serum by non-invasive procedures, has showed great potential to predict treatment response and survival for cancer patients. Several studies have assessed the prognostic and predictive value of cfDNA in non-small cell lung cancer (NSCLC). However, these studies were often small and reported varying results. To address this issue, a meta-analysis was carried out. A total of 22 studies involving 2518 patients were subjected to the final analysis. Our results indicated that NSCLC patients with higher cfDNA concentration had shorter median progression-free survival (PFS) and overall survival (OS) time. In addition, high levels of cfDNA were significantly associated with poor PFS (hazard ratio or HR, 1.32; 95% CI, 1.02-1.71) and OS (HR, 1.64; 95% CI, 1.26-2.15). With respect to tumor specific mutations, we failed to reveal significant differences for PFS (HR, 1.30; 95% CI, 0.66-2.56) and OS (HR, 1.05; 95% CI, 0.49-2.25) when NSCLC patients were grouped according to KRAS genotype detected in cfDNA. However, NSCLC patients which harbored EGFR activating mutation in cfDNA had a greater chance of response to EGFR-TKIs (odds ratio or OR, 1.96; 95% CI, 1.59-2.42). No significant publication bias was detected in this study. In conclusion, cfDNA could act as a prognostic and predictive biomarker for patients with NSCLC.

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“…In contrast, cell death in normal blood nucleated cells occurs mostly via apoptosis that generates small and uniform DNA fragments. Support for this hypothesis has been reported by several papers [ 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ] and confirmed in recent studies demonstrating increased DNA length in plasma from patients with breast [ 13 , 14 ], prostate [ 15 ], colorectal [ 16 , 17 , 18 ] and lung cancer [ 19 ].…”

Section: Introductionmentioning

confidence: 54%

Integrity and Quantity of Total Cell-Free DNA in the Diagnosis of Thyroid Cancer: Correlation with Cytological Classification

Salvianti

Giuliani

Petrone

et al. 2017

IJMS

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Cell-free DNA (cfDNA) quantity and quality in plasma has been investigated as a non-invasive biomarker in cancer. Previous studies have demonstrated increased cfDNA amount and length in different types of cancer with respect to healthy controls. The present study aims to test the hypothesis that the presence of longer DNA strands circulating in plasma can be considered a biomarker for tumor presence in thyroid cancer. We adopted a quantitative real-time PCR (qPCR) approach based on the quantification of two amplicons of different length (67 and 180 bp respectively) to evaluate the integrity index 180/67. Cell-free DNA quantity and integrity were higher in patients affected by nodular thyroid diseases than in healthy controls. Importantly, cfDNA integrity index was higher in patients with cytological diagnosis of thyroid carcinoma (Thy4/Thy5) than in subjects with benign nodules (Thy2). Therefore, cfDNA integrity index 180/67 is a suitable parameter for monitoring cfDNA fragmentation in thyroid cancer patients and a promising circulating biomarker in the diagnosis of thyroid nodules.

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Plasma cell-free DNA levels and integrity in patients with chest radiological findings: NSCLC versus benign lung nodules

Cited by 39 publications

References 36 publications

<p>Update on liquid biopsy in clinical management of non-small cell lung cancer</p>

<p>Update on liquid biopsy in clinical management of non-small cell lung cancer</p>

Circulating cell-free DNA as a prognostic and predictive biomarker in non-small cell lung cancer

Integrity and Quantity of Total Cell-Free DNA in the Diagnosis of Thyroid Cancer: Correlation with Cytological Classification

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