Screening and Triage Test for Early Detection of Gastric Cancer (STEAD-GC): A noninvasive trial for early detection of gastric cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 17-17
Author(s):  
Alejandro Corvalan ◽  
Maria Jose Maturana ◽  
Marianela Sanchez ◽  
Alfonso Calvo ◽  
Catterina Ferreccio
Keyword(s):  
Gastric Cancer ◽  
Early Detection ◽  
Dna Extraction ◽  
Mass Screening ◽  
Chronic Gastritis ◽  
Plasma Samples ◽  
Bisulfite Conversion ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Triage Test

17 Background: Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. Previously, we identified a potential biomarker for non-invasive detection of GC, the DNA methylation of the promoter region of Reprimo, a p53-dependent G2 arrest mediator candidate (Clin Cancer Res 2008;14:6264-9). Furthermore, we developed a quantitative assay (MethyLight) for a mass screening of GC (DDW2011-1029128). Here we reported the preliminary findings of our ongoing prospective trial STEAD-GC (Screening and Triage test for Early Detection of Gastric Cancer) which is being conducted in Chile, a country with a high mortality rate for GC. Methods: Twenty GC cases (tumor, non-tumor tissues and plasma samples) and 41 symptomatic chronic gastritis cases (29 tissues and 12 pairs of tissue and plasma samples) were evaluated for Reprimo levels by MethyLight after DNA extraction and bisulfite conversion. Results: Concentrations of DNA were similar in both groups (Avg 32.2 ng/ml [range: 8.9-70.8 ng/ml]). The average DNA levels of Reprimo were higher in GC [964,215 copies/ml, 539,593 copies/ml and 80,113 copies/ml in tumor, non-tumor and plasma, respectively] but lower in symptomatic chronic gastritis [137,721 copies/ml and 8,387 copies/ml, tissue and plasma, respectively]. Methods: Twenty GC cases (tumor, non-tumor tissues, and plasma samples) and 41 symptomatic chronic gastritis cases (29 tissues and 12 pairs of tissue and plasma samples) were evaluated for Reprimo levels by MethyLight after DNA extraction and bisulfite conversion. Conclusions: By using our previous cut-off of 15,125 copies/ml, our method correctly identified 10 out of 12 gastritis cases and 16 out of 20 GC cases (p value <0.001). Our data confirms our non-invasive method for early detection of GC may be suitable for a mass screening of GC.

DNR METILINIMO POKYČIAI PERIFERINIO KRAUJO LEUKOCITUOSE PACIENTAMS, SERGANTIEMS SKRANDŽIO VĖŽIU

2013 ◽  
Vol 23 (2) ◽  
pp. 66-70
Author(s):  
Albertas Daukša ◽  
Antanas Gulbinas ◽  
Aurelija Kazlauskaitė ◽  
Johannes Oldenburg ◽  
Osman El-Maarri
Keyword(s):  
Gastric Cancer ◽  
Early Detection ◽  
Peripheral Blood ◽  
Tumor Suppressor Genes ◽  
Survival Rates ◽  
Peripheral Blood Leukocyte ◽  
Blood Leukocytes ◽  
Non Invasive ◽  
Blood Leukocyte ◽  
Gastric Cancer Patients

Gastric cancers are usually diagnosed at an advanced stage in the progression of the disease, thus reducing the survival chances of the patients. Non-invasive early detection would greatly enhance therapy and survival rates. For this aim, we investigated tumor suppressor genes CDKN2A/p16, RARBeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2 and CD44 for methylation changes in peripheral blood leukocytes of gastric cancer patients. This study shows that methylation changes in peripheral blood leukocyte DNA could provide a promising method for the early detection of gastric cancer. However, larger studies are essential to explore the clinical usefulness of a peripheral blood leukocyte DNA methylation based tests for non-invasive early detection of gastric cancer.

Circulating tumor DNA methylation as markers for early detection of pancreatic ductal adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 395-395
Author(s):  
Xiaoding Liu ◽  
Shiwei Guo ◽  
Chengcheng Ma ◽  
Yatong Li ◽  
Xiaoqian Liu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Detection ◽  
Circulating Tumor Dna ◽  
Detection Methods ◽  
Ductal Adenocarcinoma ◽  
Plasma Samples ◽  
Average Sensitivity ◽  
Reduced Representation ◽  
Non Invasive ◽  
Normal Plasma

395 Background: PDAC is a cancer of high mortality and low survival. Its early detection is critical due to symptoms often occur only at advanced stages. However there is no reliable screening tool to identify high-risk patients. ctDNA methylation has recently emerged as a promising new target to differentiate PDAC plasma from normal plasma for its early detection. Methods: Reduced representation bisulfite sequencing libraries were made in 46 PDAC tissues, 30 para-PDAC tissues and 20 PDAC plasmas to screen PDAC-specific markers, which was done by quantifying and comparing methylation levels of genomic regions and individual CpG sites between those groups. Markers were validated in plasma samples from 84 PDAC patients and 64 normal controls to propose a blood classifier. The best-performing markers were developed into a targeted sequencing panel, which was tested on a larger collection of plasma samples from patients of a variety of pancreatic diseases to build and validate a PDAC-predicting model. Results: We profiled genome-wide methylation patterns of tissues samples to identify 171 PDAC-specific markers. We reiterated training and cross-validating PDAC classification models using SVM method, and achieved an average sensitivity of 86% and specificity of 88%. To prove the feasibility of a non-invasive detection in plasma, a targeted methylation assay using those markers was tested on PDAC and normal plasmas, and yielded an average sensitivity of 68.4% and a specificity of 85.8%. We refined the panel by selecting the most discriminatory markers and built the version II of the panel, which was named PANcreatic Cancer Detection Assay, or PANDA, for a more efficient target capture, which was validated in an independent cohort of plasma samples that included 94 PDAC cases, 25 chronic pancreatitis (CP) cases and 80 normal samples from multiple centers. The PANDA achieved an AUC of 0.906 when classifying PDAC from normal, and an AUC of 0.882 when separating PDAC from CPs, both of which are more accurate than CA19-9, the conventional blood marker for PDAC. We further integrated test subjects’ age and their CA19-9 level as features into the PANDA model, which further elevated their AUC to 0.882 and 0.933 when classifying PDAC plasma from either CP plasma or normal plasma, respectively. Conclusions: We have developed PANDA, an NGS based target assay covering PDAC-specific DNA methylation targets by screening and validation on PDAC tissues and plasmas. Combined with age and CA19-9 blood level, PANDA has shown encouraging results to classify PDAC plasma from non-malignant diseases, demonstrating its potential to be optimized into non-invasive diagnostics for blood-based early PDAC screening.

A noninvasive gastric cancer Her2 test using surrogate methylation markers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16084-e16084
Author(s):  
Xin Liu ◽  
Gengtai Ye ◽  
Chunhui Cui ◽  
Hui Li ◽  
Ting Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Dna Methylation ◽  
Blood Test ◽  
Her2 Status ◽  
Diagnostic Model ◽  
Plasma Samples ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Non Invasive

e16084 Background: There are 10-20% of gastric cancer (GC) with overexpressed Her2. Her2 status remains an essential biomarker for guiding the trastuzumab (Herceptin) therapy, a monoclonal antibody approved for the first-line treatment of late-stage Her2-positive GC. Although IHC, together with FISH, is comprehensively applied to verify Her2 status on tissue samples, an accurate blood test is highly desirable due to the inaccessibility of tissue samples, especially in very late stage GC patients as well as tumor heterogeneity of tissue biopsy. Detecting copy number aberration of Her2 gene in cell-free DNA (cfDNA) gains a lot of interest for its non-invasive approach. However, the limited signal-to-noise ratio poses a great challenge for the accuracy and robustness of the tests (either targeted sequencing or ddPCR). Here, we report a non-invasive test for Her2 status verification based on novel surrogate DNA methylation markers. Methods: Genome-wide DNA methylation sequencing was performed in 30 Her2-negative (IHC 0/1+) and 44 Her2-positive (IHC 3+) tissue samples to identify Her2-overexpression-specific methylation markers. Then we analyzed the performance of these candidate markers using methylation-specific quantitative PCR (qMSP) in plasma samples collected from 102 GC patients before surgical treatment. A Her2-status diagnostic model was built and further validated in a multi-center, prospective cohort (n = 150). The concordance of Her2 status between GC plasma and matching tissue samples (IHC/FISH) was determined. Results: We first discovered 102 statistically significant methylation markers of Her2 status in tissue. Out of these candidate markers, a 3-marker diagnostic model was built and validated on plasma samples, which could discriminate Her2-positive from Her2-negative GC patients with high sensitivity (86.7%) and specificity (96.8%). The overall plasma-tissue concordance of this liquid biopsy test was 95.3%. Furthermore, the Her2-status test was able to classify Her2 2+ status (IHC) into either Her2-negative or Her2-positive status, which was confirmed by conventional FISH test. Conclusions: Overall, the cfDNA-based test is a novel, accurate and noninvasive approach for determining Her2 status in GC patients. The high concordance with IHC/FISH results of this blood test holds great promise as an auxiliary method for guiding Her2-targeted therapy in GC patients. A clinical trial is undergoing to validate this test in the phase-2 clinical trial of a Her2-targeted drug (for GC) in China.

scholarly journals Identification of Serum MicroRNAs as Novel Non-Invasive Biomarkers for Early Detection of Gastric Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33608 ◽  
Author(s):  
Ming-yang Song ◽  
Kai-feng Pan ◽  
Hui-juan Su ◽  
Lian Zhang ◽  
Jun-ling Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Detection ◽  
Non Invasive ◽  
Serum Micrornas

scholarly journals P-0067 Screening and Triage test for Early Detection of Gastric Cancer (STEAD-GC)

2012 ◽  
Vol 23 ◽  
pp. iv50
Author(s):  
Alejandro Corvalan ◽  
Alfonso Calvo ◽  
Catterina Ferreccio ◽  
Maria Maturana ◽  
Paz Cook ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Detection ◽  
Triage Test

Effect of periodic endoscopy for gastric cancer on early detection and improving survival

2001 ◽  
Vol 120 (5) ◽  
pp. A606-A606
Author(s):  
Y MORII ◽  
T YOSHIDA ◽  
T MATSUMATA ◽  
T ARITA ◽  
K SHIMODA ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Detection

scholarly journals Impact of Collection Volume and DNA Extraction Method on the Detection of Biomarkers and HPV DNA in First-Void Urine

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1989
Author(s):  
Laura Téblick ◽  
Severien Van Keer ◽  
Annemie De Smet ◽  
Pierre Van Damme ◽  
Michelle Laeremans ◽  
...  
Keyword(s):  
Dna Extraction ◽  
Internal Control ◽  
Extraction Methods ◽  
Urine Collection ◽  
Hpv Dna ◽  
Non Invasive ◽  
Herpesvirus 1 ◽  
Dna Extraction Methods ◽  
Detection Of Biomarkers ◽  
High Risk Hpv

The potential of first-void (FV) urine as a non-invasive liquid biopsy for detection of human papillomavirus (HPV) DNA and other biomarkers has been increasingly recognized over the past decade. In this study, we investigated whether the volume of this initial urine stream has an impact on the analytical performance of biomarkers. In parallel, we evaluated different DNA extraction protocols and introduced an internal control in the urine preservative. Twenty-five women, diagnosed with high-risk HPV, provided three home-collected FV urine samples using three FV urine collection devices (Colli-Pee) with collector tubes that differ in volume (4, 10, 20 mL). Each collector tube was prefilled with Urine Conservation Medium spiked with phocine herpesvirus 1 (PhHV-1) DNA as internal control. Five different DNA extraction protocols were compared, followed by PCR for GAPDH and PhHV-1 (qPCR), HPV DNA, and HBB (HPV-Risk Assay), and ACTB (methylation-specific qPCR). Results showed limited effects of collection volume on human and HPV DNA endpoints. In contrast, significant variations in yield for human endpoints were observed for different DNA extraction methods (p < 0.05). Additionally, the potential of PhHV-1 as internal control to monitor FV urine collection, storage, and processing was demonstrated.

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