scholarly journals Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 522 ◽  
Author(s):  
Patricia Mondelo-Macía ◽  
Carmela Rodríguez-López ◽  
Laura Valiña ◽  
Santiago Aguín ◽  
Luis León-Mateos ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Copy Number ◽  
Patients With Cancer ◽  
Circulating Free Dna ◽  
Free Dna ◽  
Met Amplification ◽  
Potential Biomarker

MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p <10−10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch® and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET+ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.

Detection and oncological impact of circulating tumor cells in bladder cancer patients with presence of copy number variations of circulating cell free DNA.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 495-495 ◽  
Author(s):  
Armin Soave ◽  
Heidi Schwarzenbach ◽  
Malte Vetterlein ◽  
Jessica Rührup ◽  
Oliver Engel ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Copy Number ◽  
Copy Number Variations ◽  
Chromosome 8 ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna

495 Background: To investigate detection and oncological impact of circulating tumor cells (CTC) in bladder cancer patients with presence of copy number variations (CNV) of circulating cell-free DNA (cfDNA) treated with radical cystectomy (RC). Methods: Secondary analysis of 85 bladder cancer patients, who were prospectively enrolled and treated with RC at our institution between 2011 and 2014. Blood samples were obtained preoperatively. For CTC analysis, blood was analyzed with the CellSearch system (Janssen). cfDNA was extracted from serum using the PME DNA Extraction kit (Analytik Jena). Multiplex ligation-dependent probe amplification (MLPA) was carried out to identify CNV of cfDNA. In a single reaction MLPA allows analyzing CNV in 43 chromosomal regions containing 37 genes. Results: MLPA was suitable for characterization of CNV in 72 patients (84.7%). Data on CTC was available for 45 of these patients (62.5%). In total, 7 patients (15.6%) had CTC with a median CTC count of one (IQR: 1-3). In 21 patients (46.7%), one to 6 deleted or amplified chromosomal regions were detected with a median CNV count of 2 (IQR: 1-2). Overall, most changes were located in the genes CDH1, RIPK2 and ZFHX3 in 8 patients (17.8%), 6 patients (13.3%) and 5 patients (11.1%). Chromosomal aberrations were most frequently found on chromosome 8 in 8 patients (17.8%). Overall, presence of CTC was not associated with CNV status. However, presence of CTC was associated with copy number losses in miR-15a (p = 0.011). Patients with CTC had reduced recurrence-free survival (RFS) compared to patients without CTC (p = 0.012). In combined Kaplan-Meier analysis, patients with CTC plus presence of CNV had reduced cancer-specific survival (CSS) and RFS compared to patients without CTC but with presence of CNV (p≤0.035). In addition, patients with CTC plus presence of CNV had reduced RFS compared to patients without CTC and without presence of CNV (p = 0.028). Conclusions: CTC and CNV of various genes are detectable in peripheral blood of bladder cancer patients. The presence of CTC seems to be associated with CNV of specific genes. CTC have a negative impact on survival in patients with and without presence of CNV.

scholarly journals Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Pengjie Yu ◽  
Shengmao Zhu ◽  
Yushuang Luo ◽  
Ganggang Li ◽  
Yongqiang Pu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Advanced Gastric Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Circulating Free Dna ◽  
Free Dna ◽  
N Stage

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

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