scholarly journals Liver- and Colon-Specific DNA Methylation Markers in Plasma for Investigation of Colorectal Cancers with or without Liver Metastases

2018 ◽  
Vol 64 (8) ◽  
pp. 1239-1249 ◽  
Author(s):  
Wanxia Gai ◽  
Lu Ji ◽  
W K Jacky Lam ◽  
Kun Sun ◽  
Peiyong Jiang ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Liver Cancer ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Transplant Recipients ◽  
Fractional Concentration ◽  
Liver Transplant Recipients

Abstract BACKGROUND Measurement of DNA derived from different tissues in the circulating DNA pool can provide important information regarding the presence of many pathological conditions. However, existing methods involving genome-wide bisulfite sequencing are relatively expensive and may present challenges for large-scale analysis. METHODS Through identifying differentially methylated regions in the liver and colon compared with other tissues, we identified 2 markers and developed corresponding droplet digital PCR assays. Plasma concentrations of liver-derived and colon-derived DNA were measured for 13 liver transplant recipients, 40 liver cancer patients, and 62 colorectal cancer (CRC) patients (27 with and 35 without liver metastases). RESULTS In liver transplant recipients, the fractional concentration of liver-derived DNA measured using the liver-specific methylation marker and donor-specific alleles showed good correlation (Pearson R = 0.99). In liver cancer patients, the concentration of liver-derived DNA correlated positively with the maximal dimension of the tumor (Spearman R = 0.74). In CRC patients with and without liver metastasis, the plasma concentrations of colon-derived DNA (median, 138 copies/mL and 4 copies/mL, respectively) were increased compared with the 30 healthy controls (26 had undetectable concentrations). The absolute concentration of liver-derived DNA provided a better differentiation between CRC patients with and without liver metastasis compared with the fractional concentration (area under ROC curve, 0.85 vs 0.75). CONCLUSIONS Quantitative analysis of plasma DNA with tissue-specific methylation patterns using droplet digital PCR is applicable for the investigation of cancers and assessing organ transplantation. This approach is useful for differentiating patients with and without metastases to other organs.

PO-097: Droplet Digital PCR for detection of circulating tumour DNA in blood of head and neck cancer patients

2017 ◽  
Vol 122 ◽  
pp. 46
Author(s):  
J.H. Van Ginkel ◽  
M.M.H. Huibers ◽  
R.J.J. Van Es ◽  
R. De Bree ◽  
S.M. Willems
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Circulating Tumour Dna

scholarly journals Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Joost H. van Ginkel ◽  
Manon M. H. Huibers ◽  
Robert J. J. van Es ◽  
Remco de Bree ◽  
Stefan M. Willems
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Droplet Digital Pcr ◽  
Tumor Dna ◽  
Detection And Quantification

scholarly journals Droplet Digital PCR Analysis of Liquid Biopsy Samples Unveils the Diagnostic Role of hsa-miR-133a-3p and hsa-miR-375-3p in Oral Cancer

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 379
Author(s):  
Salvatore Crimi ◽  
Luca Falzone ◽  
Giuseppe Gattuso ◽  
Caterina Maria Grillo ◽  
Saverio Candido ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Pcr Analysis ◽  
Screening Programs ◽  
Diagnostic Potential ◽  
Oral Cancer Patients

Despite the availability of screening programs, oral cancer deaths are increasing due to the lack of diagnostic biomarkers leading to late diagnosis and a poor prognosis. Therefore, there is an urgent need to discover novel effective biomarkers for this tumor. On these bases, the aim of this study was to validate the diagnostic potential of microRNAs (miRNAs) through the analysis of liquid biopsy samples obtained from ten oral cancer patients and ten healthy controls. The expression of four selected miRNAs was evaluated by using droplet digital PCR (ddPCR) in a pilot cohort of ten oral cancer patients and ten healthy donors. Bioinformatics analyses were performed to assess the functional role of these miRNAs. The expression levels of the predicted down-regulated hsa-miR-133a-3p and hsa-miR-375-3p were significantly reduced in oral cancer patients compared to normal individuals while no significant results were obtained for the up-regulated hsa-miR-503-5p and hsa-miR-196a-5p. ROC analysis confirmed the high sensitivity and specificity of hsa-miR-375-3p and hsa-miR-133a-3p. Therefore, both miRNAs are significantly down-regulated in cancer patients and can be used as biomarkers for the early diagnosis of oral cancer. The analysis of circulating miRNAs in a larger series of patients is mandatory to confirm the results obtained in this pilot study.

scholarly journals Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Ryan M. Rivosecchi ◽  
Cornelius J. Clancy ◽  
Ryan K. Shields ◽  
Christopher R. Ensor ◽  
Michael A. Shullo ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Organ Transplant ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Dose Ratio ◽  
Transplant Patients ◽  
Daily Dose ◽  
Liver Transplant Recipients

ABSTRACT We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable interpatient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly but, rather, be guided by therapeutic drug monitoring.

scholarly journals Quantitative Cell-Free Circulating BRAFV600E Mutation Analysis by Use of Droplet Digital PCR in the Follow-up of Patients with Melanoma Being Treated with BRAF Inhibitors

2015 ◽  
Vol 61 (1) ◽  
pp. 297-304 ◽  
Author(s):  
Miguel F Sanmamed ◽  
Sara Fernández-Landázuri ◽  
Carmen Rodríguez ◽  
Ruth Zárate ◽  
María D Lozano ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Progression Free Survival ◽  
Digital Pcr ◽  
Tumor Burden ◽  
Advanced Melanoma ◽  
Droplet Digital Pcr ◽  
Brafv600e Mutation ◽  
Braf Inhibitors ◽  
Best Response

Abstract BACKGROUND Around 50% of cutaneous melanomas harbor the BRAFV600E mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAFV600E (cfBRAFV600E). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAFV600E by ddPCR in patients with melanoma during therapy with BRAF inhibitors. METHODS Plasma concentrations of cfBRAFV600E were measured in 8 controls and 20 patients with advanced melanoma having the BRAFV600E mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression. RESULTS The BRAFV600E mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAFV600E and plasma cfBRAFV600E was 84.3%. Baseline cfBRAFV600E correlated with tumor burden (r = 0.742, P < 0.001). cfBRAFV600E concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1–Q3, 27–647 copies/mL; first response median, 0 copies/mL; Q1–Q3, 0–49 copies/mL; P < 0.01) and at the moment of best response (median, 0 copies/mL; Q1–Q3, 0–33 copies/mL; P < 0.01). At progression, there was a significant increase in the concentration of cfBRAFV600E compared with best response (median, 115 copies/mL; Q1–Q3, 3–707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAFV600E were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P < 0.001 and P = 0.024, respectively). CONCLUSIONS cfBRAFV600E quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.

scholarly journals Droplet digital PCR of circulating tumor cells from colorectal cancer patients can predictKRASmutations before surgery

2016 ◽  
Vol 10 (8) ◽  
pp. 1221-1231 ◽  
Author(s):  
Jérôme Alexandre Denis ◽  
Alexia Patroni ◽  
Erell Guillerm ◽  
Dominique Pépin ◽  
Naoual Benali-Furet ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Colorectal Cancer Patients

scholarly journals High-Throughput Detection of Multiple miRNAs and Methylated DNA by Droplet Digital PCR

2021 ◽  
Vol 11 (5) ◽  
pp. 359
Author(s):  
Ning Li ◽  
Pushpa Dhilipkannah ◽  
Feng Jiang
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Cancer Patients ◽  
High Throughput ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Lung Cancer Patients ◽  
Molecular Aberrations ◽  
High Throughput Assay

Altered miRNA expression and DNA methylation have highly active and diverse roles in carcinogenesis. Simultaneous detection of the molecular aberrations may have a synergistic effect on the diagnosis of malignancies. Herein, we develop a high-throughput assay for detecting multiple miRNAs and DNA methylation using droplet digital PCR (ddPCR) coupled with a 96-microwell plate. The microplate-based ddPCR could absolutely and reproducibly quantify 15 miRNAs and 14 DNA methylation sites with a high sensitivity (one copy/µL and 0.1%, respectively). Analyzing sputum and plasma of 40 lung cancer patients and 36 cancer-free smokers by this approach identified an integrated biomarker panel consisting of two sputum miRNAs (miRs-31-5p and 210-3p), one sputum DNA methylation (RASSF1A), and two plasma miRNAs (miR-21-5p and 126) for the diagnosis of lung cancer with higher sensitivity and specificity compared with a single type of biomarker. The diagnostic value of the integrated biomarker panel for the early detection of lung cancer was confirmed in a different cohort of 36 lung cancer patients and 39 cancer-free smokers. The high-throughput assay for quantification of multiple molecular aberrations across sputum and plasma could improve the early detection of lung cancer.

Use of droplet digital PCR for quantitative and automatic analysis of the HER2 status in breast cancer patients

2016 ◽  
Vol 162 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Kazutaka Otsuji ◽  
Takeshi Sasaki ◽  
Atsushi Tanaka ◽  
Akiko Kunita ◽  
Masako Ikemura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Automatic Analysis ◽  
Her2 Status ◽  
Breast Cancer Patients

scholarly journals Incidence and Prognostic Significance of Liver Metastases for Newly Diagnosed Ovarian Cancer in Relation to Subtypes

2021 ◽  
Author(s):  
Ying Zhu ◽  
Yifang Zhang ◽  
Lingyun Zhai ◽  
Zhigang Zhang ◽  
Jianwei Zhou
Keyword(s):  
Ovarian Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Newly Diagnosed ◽  
Histological Types ◽  
Visceral Organs

Abstract Background: Ovarian cancer is a heterogeneous and aggressive malignant tumor, and the liver is one of the most common metastases target visceral organs of ovarian cancer. We aim to analysis the incidence and prognostic relevance of histological subtypes for patients with liver metastases in newly diagnosed ovarian cancer. Methods: In the Surveillance, Epidemiology, and End Results (SEER) database, we identified the ovarian cancer patients from 2010 to 2016. Multivariable logistic regression was used to determine whether histological types were associated with the presence of liver metastases at diagnosis. The Kaplan-Meier method and multivariable Cox regression was performed to identify covariates associated with survival using the histological types. Results: Among 25293 ovarian cancer patients, 1749 cases presented with liver metastases. The incidence proportions were highest among ovarian carcinosarcoma patients (OR=17.76, 95% CI=9.26-34.09), and liver metastasis specificity was the highest in the clear cell type (70.69% of the metastatic subset). The median cancer-specific survival (CSS) for non-metastatic ovarian cancer patients was 77 months, but the ovarian cancer with only liver metastasis was 21 months. The mucinous (5 months; vs nonepithelial subtype, HR=0.26; 95% CI, 0.14-0.49) subtype experienced the shortest median survival among all histologic types. Conclusion: This population-based study provides that liver was one of the most common distant visceral organs for ovarian cancer metastasis, and the incidence proportions of liver metastasis were highest for carcinosarcomas subtype, and the mucinous ovarian cancer with liver metastasis being associated with the poorest survival.

Sign in / Sign up

Export Citation Format

Share Document