Combined use of methylated reprimo cell-free DNA and pepsinogens for noninvasive detection of early gastric cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 27-27
Author(s):  
Alejandra Alarcon ◽  
Wilda Olivares ◽  
Maria Jose Maturana ◽  
Andres Rodriguez ◽  
Oslando Padilla ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Sensitivity And Specificity ◽  
Detection Rate ◽  
Low Grade ◽  
Cell Free Dna ◽  
Predictive Values ◽  
Non Invasive ◽  
Free Dna ◽  
Combined Use ◽  
Potential Biomarker

27 Background: Gastric cancer (GC) has been described as a multistep cascade of precursor lesions such as non-atrophic chronic gastritis (NACG), multiphocal atrophic gastritis (MAG), intestinal metaplasia (IM), low grade dysplasia (LGD) and high grade dysplasia (HGD) leading to early stages of GC (EGC). Currently, no non-invasive biomarkers for this progression are clinically available. We have previously identified a potential biomarker based on methylated Reprimo (RPRM) cell-free DNA (cfDNA) (Clin Cancer Res 2008;14:6264-9). In a cross-sectional study of 1,076 patients, we showed a sensitivity of 70.8% (95% CI: 60.3 to 81.3) and specificity of 74.3% (95% CI: 71.5 to 77) for methylated RPRM cfDNA, to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC (Digestive Disease Week 2014 #108). However, the crude detection rate of EGC was only 46.6%. Here, we aim to explore the role of the combined use of methylated RPRM cfDNA and well stablished atrophy biomarkers such as pepsinogens, for non-invasive detection of EGC. Methods: A case-control study was performed including 237 patients (NACG:40; MAG:94; IM:55; LGD:11; HGD:5: EGC:15; AGC:17) scheduled for upper gastrointestinal endoscopy (UGIE). A heparinized venous blood sample was collected and methylated RPRM cfDNA and Immunoassays for Pepsinogen I and II were performed. Positive value was considered if methylated RPRM cfDNA > 0 copies/mL and PG I/II ratio <3.0 were found. Results: Overall sensitivity and specificity for the combined use of methylated RPRM cfDNA and PGI/II to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC was 67.5% (95% CI: 50.2% to 81.9%) and 63% (95% CI: 55.9% to 69.7%), respectively. Positive and negative predictive values were 25.2% (95% CI: 17% to 34.9%) and 91.3% (95% CI: 85.3% to 95.4%), respectively. Importantly, crude detection rate for EGC increased from 46.6% to 86.7%. Conclusions: The combined use of methylated RPRM cfDNA and PGI/II reached similar sensitivity and specificity compared to methylated RPRM cfDNA alone to distinguish NACG+MAG+IM+LGD vs HGD+EGC+AGC. However, combined use of methylated RPRM cfDNA and PGI/II significantly improved the detection rate of EGC, a lesion with a curability rate over 95%.

Tu1910 Methylated Cell-Free DNA of Reprimo in Plasma for Non-Invasive Diagnosis of Gastric Cancer and Dysplasia

2013 ◽  
Vol 144 (5) ◽  
pp. S-878
Author(s):  
Teresa Martinez ◽  
Maria J. Maturana ◽  
Jacqueline Fry ◽  
Maria Mercedes Bravo ◽  
Gustavo Hernandez ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna

Clinical Accuracy and Impact of Plasma Cell-Free DNA Fungal PCR Panel for Non-Invasive Diagnosis of Fungal Infection

2021 ◽  
Author(s):  
Fiona Senchyna ◽  
Catherine A Hogan ◽  
Kanagavel Murugesan ◽  
Angel Moreno ◽  
Dora Y Ho ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Sensitivity And Specificity ◽  
Positive Impact ◽  
Diagnostic Methods ◽  
Fungal Cell ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Non Invasive ◽  
Free Dna ◽  
Pcr Targeting

Abstract Background Invasive fungal infection (IFI) is a growing cause of morbidity and mortality in oncology and transplant patients. Diagnosis of IFI is often delayed due to need for invasive biopsy and low sensitivity of conventional diagnostic methods. Fungal cell-free DNA (cfDNA) detection in plasma is a novel testing modality for the non-invasive diagnosis of IFI. Methods A novel bioinformatic pipeline was created to interrogate fungal genomes and identify multicopy sequences for cfDNA PCR targeting. A real-time PCR panel was developed for 12 genera and species most commonly causing IFI. Sensitivity and specificity of the fungal PCR panel were determined using plasma samples from patients with IFI and non-IFI controls. Clinical impact of fungal PCR panel was evaluated prospectively based on the treating team’s interpretation of the results. Results Overall, the sensitivity and specificity were 56.5% (65/115, 95% confidence interval [CI], 47.4%-65.2%) and 99.5% (2064/2075; 95% CI, 99.0%-99.7%), respectively. In the subset of patients with an optimized plasma volume (2mL), sensitivity was 69.6% (48/69; 95% CI, 57.9%-79.2%). Sensitivity was 91.7% (11/12; 95% CI, 62.5%-100%) for detection of Mucorales agents, 56.3% (9/16; 95% CI, 33.2%-76.9%) for Aspergillus species, and 84.6% (11/13; 95% CI, 56.5%-96.9%) for Candida albicans. In a prospective evaluation of 226 patients with suspected IFI, cfDNA testing was positive in 47 (20.8%) patients and resulted in a positive impact on clinical management in 20/47 (42.6%). Conclusions The fungal cfDNA PCR panel offers a non-invasive approach to early diagnosis of IFI, providing actionable results for personalized care.

scholarly journals Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Specific Patient ◽  
Free Dna ◽  
Potential Biomarker ◽  
Cancer Types

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.

scholarly journals 670. Rapid, Non-invasive Detection of Invasive Mycoplasma hominis Infection using the Karius Test, A Next-Generation Sequencing Test for Microbial Cell-free DNA in Plasma

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S390-S390
Author(s):  
Priya Edward ◽  
William V La Via ◽  
Mehreen Arshad ◽  
Kiran Gajurel
Keyword(s):  
Next Generation Sequencing ◽  
Case Series ◽  
Mycoplasma Hominis ◽  
Microbial Cell ◽  
Next Generation ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Hominis Infection ◽  
Generation Sequencing

Abstract Background Mycoplasma hominis is typically associated with genital infections in women and is a rare cause of musculoskeletal infections often in immunocompromised hosts. Diagnosis of invasive Mycoplasma hominis infections are difficult due to challenges in culturing these organisms. Molecular diagnostics require an index of suspicion which may not be present at the time of tissue sampling. Accurate, rapid diagnosis of Mycoplasma hominis infections are important for antibiotic management. Methods Two cases of invasive Mycoplasma hominis infections are presented in which the Karius test (KT) was used to make the diagnosis. The KT is a CLIA certified/CAP-accredited next-generation sequencing (NGS) plasma test that detects microbial cell-free DNA (mcfDNA). After mcfDNA is extracted and NGS performed, human reads are removed and remaining sequences are aligned to a curated database of &gt; 1400 organisms. Organisms present above a statistical threshold are reported. Case review was performed for clinical correlation. Results A young woman with lupus nephritis status post renal transplant developed persistent fever with progressive multifocal culture-negative osteoarticular infection despite empiric ceftriaxone. An adolescent female presented with an ascending pelvic infection progressing to purulent polymicrobial peritonitis (see table) requiring surgical debridement and cefipime, metronidazole and micafungin therapy; her course was complicated by progressive peritonitis/abscesses. Karius testing detected high-levels of Mycoplasma hominis mcfDNA in both cases – at 3251 molecules/microliter (MPM) in the first case and 3914 MPM in the second case. The normal range of Mycoplasma hominis mcfDNA in a cohort of 684 normal adults is 0 MPM. The patients rapidly improved with atypical coverage with doxycycline and levofloxaxin. Clinical findings in 2 patients with M. hominis infection detected by the Karius Test Conclusion Open-ended, plasma-based NGS for mcfDNA provides a rapid, non-invasive method to diagnose invasive Mycoplasma hominis infection. This case series highlights the potential to diagnose infections caused by fastidious pathogens to better inform antimicrobial therapy and achieve favorable outcomes. Disclosures William V. La Via, MD, Karius (Employee)

scholarly journals Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Troponin I ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Predictive Values ◽  
Non Invasive ◽  
Potential Biomarker

AbstractMyocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

Is there still a rationale for non-invasive PGT-A by analysis of cell-free DNA released by human embryos into culture medium?

2021 ◽  
Vol 36 (5) ◽  
pp. 1186-1190
Author(s):  
Raoul Orvieto ◽  
Adva Aizer ◽  
Norbert Gleicher
Keyword(s):  
Culture Media ◽  
Chromosomal Rearrangements ◽  
Primary Source ◽  
Normal Pregnancy ◽  
Early Embryo ◽  
Human Embryos ◽  
Cell Debris ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna

Abstract Human embryos utilise an array of processes to eliminate the very high prevalence of aneuploid cells in early embryo stages. Human embryo self-correction was recently demonstrated by their ability to eliminate/expel abnormal blastomeres as cell debris/fragments. A whole genome amplification study has demonstrated that 63.6% of blastocysts expelled cell debris with abnormal chromosomal rearrangements. Moreover, 55.5% of euploid blastocysts expel aneuploid debris, strongly suggesting that the primary source of cell free DNA in culture media is expelled aneuploid blastomeres and/or their fragments. Such a substantial ability to self-correct downstream from the blastocyststage, therefore, renders any chromosomal diagnosis at the blastocyststage potentially useless, and this, unfortunately, also must particularly include non-invasive PGT-A based on cell-free DNA in spent medium. High rates of false-positive diagnoses of human embryos often lead to non-use and/or disposal of embryos with entirely normal pregnancy potential. Before adopting yet another round of unvalidated PGT-A as a routine adjunct to IVF, we here present facts that deserve to be considered.

scholarly journals Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Brian C.-H. Chiu ◽  
Chang Chen ◽  
Qiancheng You ◽  
Rudyard Chiu ◽  
Girish Venkataraman ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Non Invasive ◽  
Signature Genes ◽  
Non Hodgkin Lymphoma ◽  
Free Dna ◽  
Genome Wide ◽  
Circulating Cell Free Dna

AbstractThe 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.

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