scholarly journals 5-Hydroxymethylcytosine Profiles in Plasma Cell-free DNA Reflect Molecular Characteristics of Diabetic Kidney Disease

2022 ◽  
Author(s):  
Jin-Lin Chu ◽  
Shu-Hong Bi ◽  
Yao He ◽  
Rui-Yao Ma ◽  
Xing-Yu Wan ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Diabetic Kidney Disease ◽  
Marker Genes ◽  
Hub Genes ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Diabetic Kidney ◽  
Non Invasive ◽  
Free Dna

Abstract Background: Complications of diabetes mellitus (DM) are the leading cause of DM-related disability and mortality. Notably, diabetic kidney disease (DKD), one of the main complications of DM, has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions.Methods: We utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially modified 5hmC marker genes (DMGs) and differentially expressed genes (DEGs) from the GEO datasets GSE30528 and GSE30529. Cytoscape software was used to construct the protein-protein interaction (PPI) network and identify the hub genes.Results: The final gene panel of 9 hub genes, including (CTNNB1, PTEN, MYD88, ITGAM, CD28, ITGB2, VCAM1, CXCR4, CD44) were confirmed. Further analysis indicated that this 9-gene signature showed a good capacity to distinguish between DKD and DM. Conclusions: The 5hmC-Seal assay was successfully applied to the cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures in plasma cfDNA indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and be a part of diabetic care.

scholarly journals Serum cell-free DNA and progression of diabetic kidney disease: a prospective study

2020 ◽  
Vol 8 (1) ◽  
pp. e001078 ◽  
Author(s):  
Xuan Li ◽  
RenZhi Hu ◽  
Ting Luo ◽  
Chuan Peng ◽  
Lilin Gong ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Prospective Study ◽  
Diabetic Kidney Disease ◽  
High Sensitivity ◽  
Cell Free Dna ◽  
Diabetic Kidney ◽  
Reactive Protein ◽  
Free Dna ◽  
A Prospective Study

AimsCell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD).MethodsIn this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression.ResultsIn total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=−0.219 p=0.009) and 3-year eGFR change (r=−0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89).ConclusionSerum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

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.

scholarly journals The fragmentation patterns of maternal plasma cell‐free DNA and its applications in non‐invasive prenatal testing

2020 ◽  
Vol 40 (8) ◽  
pp. 911-917 ◽  
Author(s):  
Min Pan ◽  
Pingsheng Chen ◽  
Jiafeng Lu ◽  
Zhiyu Liu ◽  
Erteng Jia ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Fragmentation Patterns

scholarly journals SO004IDENTIFICATION OF HUB GENES, FOCUSED ON CHEMOKINES AND CHEMOKINE RECEPTORS, ASSOCIATED WITH THE DECLINE OF RENAL FUCTION OF DIABETIC KIDNEY DISEASE BY WEIGHTED GENE CO-EXPRESSION NETWORK ANALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Songtao Feng ◽  
Bicheng Liu ◽  
Linli Lv ◽  
Gao Yueming ◽  
Di Yin ◽  
...  
Keyword(s):  
Renal Function ◽  
Network Analysis ◽  
Kidney Disease ◽  
T Cell Activation ◽  
Chemokine Receptors ◽  
Diabetic Kidney Disease ◽  
Expression Level ◽  
Hub Genes ◽  
Diabetic Kidney ◽  
Gene Modules

Abstract Background and Aims The fact that activation of the innate immune system and chronic inflammation are closely involved in the pathogenesis of diabetic Kidney disease (DKD). Recent studies have suggested the inflammatory process plays a crucial role in the progression of DKD. Identifying novel inflammatory molecules closely related to the decline of renal function is of significance in diagnosing and predicting the progression of DKD. The weighted gene co-expression network analysis (WGCNA) algorithm represents a novel systems biology method that provide the approach of association between gene modules and clinical traits to find the genes involvement into the certain phenotypic trait. The goal of this study was to identify hub genes and their roles in DKD from the gene sets associated with the decline of renal function by WGCNA. Method The Gene Expression Omnibus (GEO) database and “Nephroseq” website were searched and transcriptome study from DN biopsies with well-established clinical phenotypic data were selected for analysis. Next, we constructed a weighted gene co-expression network and identified modules negatively correlated with eGFR by WGCNA in the data of glomerular tissue. Functional annotations of the genes in modules negatively correlated with eGFR were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Through protein-protein interaction (PPI) analysis and hub gene screening, the hub genes were obtained. Furthermore, we compared the expression level of hub genes between DKD and normal control and drew ROC curves to determine the diagnosis value to DKD of these genes. Results The microarray-based expression datasets GSE30528 were screened out for analysis, which included glomeruli tissue of 9 cases of DKD and 13 cases of control. This microarray platform represented the transcriptome profile of 12411 well-characterized genes. Using WGCNA, a total of 19 gene modules were identified. Then module eigengene were analyzed for correlation with clinical traits of age, sex, ethnicity and eGFR and the “MEhoneydew1” module showed negative associated with eGFR (r=-0.58). GO functional annotation showed that these 551 genes in the “MEhoneydew1” module mainly enriched in the T cell activation. KEGG annotation showed mainly enriched in chemokine signaling pathway. Except for C3, top 10 hub genes, CCR5, CXCR4, CCR7, CCL5, CXCL8, CCR2, CCR1, CX3CR1, C3AR1 and C3, are all members of chemokines or chemokine receptors. Furthermore, we compared the expression level of these 9 genes between DKD and control, and found that all of these 9 genes increased in the DKD group, and the differences of 6 genes, CCR5, CCR7, CCL5, CCR2, CCR1, C3AR1, were of statistical significance. Linear correlation analysis showed that the expression of these 6 genes was negatively correlated with eGFR, and the ROC curve showed that the area under the curve could reach 0.812∼1.0. Conclusion We identified a panel of 6 hub genes focused on chemokines and chemokine receptors critical for decline of renal function of DKD using WGCNA. These genes may serve as biomarkers for diagnosis/prognosis and as putative novel therapeutic targets for DKD.

Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 103-103
Author(s):  
Nicolas Guibert ◽  
Greg Jones ◽  
John F. Beeler ◽  
Clive D. Morris ◽  
Vincent Plagnol ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Plasma Cell ◽  
Progressive Disease ◽  
Genetic Alterations ◽  
Targeted Sequencing ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Free Dna ◽  
Poor Outcomes ◽  
Immune Score

103 Background: Tumor mutational burden is an emerging biomarker of response to immune checkpoint inhibitors (ICI), whose clinical adoption is challenging, especially in liquid biopsies. We hypothesized that targeting limited but relevant genetic alterations in plasma cell-free DNA with next generation sequencing (NGS) along with early monitoring may represent a non-invasive approach to predict response to ICI. Methods: Plasma samples from responders (PFS > 6 months) and non-responders (progressive disease at first evaluation) patients collected before nivolumab (second line) initiation and at 1 month were tested using tagged amplicon sequencing of hotspots and coding regions from 36 genes, blinded to clinical outcomes and tumor genotype. Molecular profile of ctDNA, and its early kinetics (1 month) were analyzed as potential early indicators of response. Results: 98 patients were analyzed, of which 86 (39 responders, 47 non-responders) were evaluable for response. Alterations in ctDNA were detectable in 67/86 baseline samples (78%). The detection of a targetable oncogenic driver (5 EGFR, 1 ALK) was associated with progressive disease on the first CT-scan The presence of a PTEN and/or STK11 mutations (b-PS(+)) was correlated with poor outcomes (median PFS 1.5 months vs. 8 months in b-PS(-)) patients, p = 0.0007), while the presence of transversion mutations in KRAS and/or TP53 (b-KP-Tv(+)) predicted good outcomes (median PFS 11 months vs. 2 months in b-KP-Tv(-) patients, p = 0.0088). Combining these results, patients with a low “immune score” (driver and/or b-PS(+) and/or b-KP-Tv(-)) derived poor outcomes (PFS 2 months), compared with patients with a high immune score (no driver, b-PS(-) and b-KP-Tv(+), PFS 14 months, p = 0.0001, HR 2.96). Studying early changes in 65 specimens, molecular response was correlated with clinical outcomes (14 months PFS in patients with early ctDNA decrease compared to 2 months in patients with increase, p < 0.0001; HR 2.7). Using cut-off of 30% and 50% of plasma response increased the ability of ctDNA to predict response (HR 4 and 4.17, respectively). Conclusions: Targeted sequencing of plasma ctDNA and its early variations can predict response to anti-PD-1. Clinical trial information: NCT02827344.

scholarly journals P-67 Early aneuploidy detection by means of QF-PCR using uterine fetal cell free DNA: A non-invasive approach

2013 ◽  
Vol 26 ◽  
pp. S52
Author(s):  
S. Zeinali ◽  
F. Savadkoohi ◽  
A. Farzad ◽  
H. Bagherian ◽  
S. Sarhadi ◽  
...  
Keyword(s):  
Fetal Cell ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Non Invasive ◽  
Free Dna

FP491MAGNETIC RESONANCE IMAGING ALLOWS A NOVEL NON-INVASIVE FUNCTIONAL AND PATHOPHYSIOLOGIC ASSESSMENT OF DIABETIC KIDNEY DISEASE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Kianoush Makvandi ◽  
Gert Jensen ◽  
Paul Hockings ◽  
Tim Unnerstall ◽  
Henrik Leonhardt ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Resonance Imaging ◽  
Diabetic Kidney ◽  
Non Invasive

scholarly journals Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC: Correlation with paired tumor samples

Oncotarget ◽  
2015 ◽  
Vol 6 (31) ◽  
pp. 30850-30858 ◽  
Author(s):  
Hidenobu Ishii ◽  
Koichi Azuma ◽  
Kazuko Sakai ◽  
Akihiko Kawahara ◽  
Kazuhiko Yamada ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasma Cell ◽  
Digital Pcr ◽  
Resistance Mechanisms ◽  
Pcr Analysis ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Egfr Mutant

scholarly journals P0218SHEAR WAVE ELASTOGRAPHY AS A NON-INVASIVE MARKER OF RENAL FIBROSIS IN NATIVE DIABETIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Charmaine Sia ◽  
Emmett Wong Tsz Yeung Wong ◽  
Christopher Cheang Han Leo ◽  
Weng Kin Wong ◽  
Boon Wee Teo ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Strong Correlation ◽  
Renal Fibrosis ◽  
Diabetic Kidney Disease ◽  
Left Kidney ◽  
Reference Method ◽  
Invasive Technique ◽  
Diabetic Kidney ◽  
Non Invasive ◽  
Native Kidney

Abstract Background and Aims Current assessment of diabetic kidney disease (DKD) is limited to estimated glomerular filtration rate (eGFR) and albuminuria. These are inadequate as DKD often has heterogenous clinical phenotypes. There is need for a marker of intra-renal fibrosis. Native kidney biopsy remains the only reference method in clinical practice for this purpose, but is invasive and impractical for repeated evaluations. Recently, two-dimensional ultrasound shear wave elastography (SWE) has emerged as a non-invasive technique to assess renal parenchymal stiffness with renal fibrosis. We aim to investigate SWE-derived estimates of tissue stiffness with different DKD stages in an Asian population. Method In this cross-sectional pilot study, 58 patients with DKD were recruited from a single centre ambulatory Nephrology clinic. Laboratory values were taken within 1 week of undergoing SWE, with DKD staging by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines and eGFR calculated using the CKD-EPI equation. 13 patients had histological diagnoses of DKD; 2 (15.3%) Stage G1-2; 5 (38.5%) Stage G3; 5 (38.5%) Stage G4 and 1 (7.7%) Stage G5 subjects, with native kidney biopsies performed within 4 months of study recruitment. 2D SWE was performed with a 2-5 MHz transducer on an Axiplorer© ultrasound system (Supersonic Imagine, Paris) by a single Nephrologist blinded to laboratory results. Using a previously described protocol, 6 SWE measurements were taken from the cortical mid-pole of bilateral kidneys, and renal elasticity estimated as Young’s Modulus (YM) in kilopascals (kPa), (Figure 1). Results Study population were 62.1% male (36/58) and 62.1% ethnic Chinese (36/58), with diabetes duration of 11.7 ± 9.2 years. Median eGFR was 35.0 (40-101) mL/min per 1.73 m2, with 6 (10.3%) DKD Stage G1-2; 34 (58.6%) Stage G3; 13 (22.4%) Stage G4 and 5 (8.6%) Stage G5 patients. There were moderate correlations between YM values in bilateral kidneys. Left kidney maximal YM generally increased in accordance with DKD stage (Stage G1-2: 20.6 kPa, Stage G3A: 13.5 kPa, Stage G3B: 22.4 kPa, Stage G4-5: 30.9 kPa, p &lt;0.01). Kidney depth correlated moderately with body mass index (BMI). After controlling kidney depth and BMI, there was a moderately positive correlation between right kidney YM and DKD stage (Maximal YM; r = 0.4, p &lt; 0.01, Mean YM; r = 0.31, p = 0.02). eGFR negatively correlated with bilateral kidney maximal YM (right r = -0.2, p = 0.04, and left r = -0.3, p = 0.03, respectively). Importantly, there was a strong correlation between right kidney mean YM and histological grading of interstitial fibrosis and tubular atrophy (r = 0.9, p = 0.01). There is no correlation between kidney elasticity and percentage of sclerosed glomeruli. Using a cut-off of 13.5 kPa for mean estimated tissue YM, the area under the receiver operator curve was 0.8 to distinguish DKD Stage G1 and G2 from G3A (sensitivity 83.3%, specificity 80.0%). Conclusion SWE-derived estimates of renal stiffness appear to increase with DKD stage. The strong correlation with histological markers of fibrosis indicate that observed differences are due to renal parenchymal stiffness. SWE shows promise as a non-invasive marker of renal fibrosis, although large multi-centre studies are required to validate these findings.

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