scholarly journals Urine miR-21-5p as a potential non-invasive biomarker for gastric cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (34) ◽  
pp. 56389-56397 ◽  
Author(s):  
Hsiao-Wei Kao ◽  
Chao-Yu Pan ◽  
Chun-Hung Lai ◽  
Chew-Wun Wu ◽  
Wen-Liang Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Non Invasive

scholarly journals The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer

2020 ◽  
Vol 21 (24) ◽  
pp. 9472
Author(s):  
María Alarcón ◽  
Wilda Olivares ◽  
Miguel Córdova-Delgado ◽  
Matías Muñoz-Medel ◽  
Tomas de Mayo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cancer Biology ◽  
Area Under The Curve ◽  
Soft Agar ◽  
Poor Overall Survival ◽  
Clinicopathologic Characteristics ◽  
Non Invasive

Reprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Here, we evaluated the role of RPRML and whether its regulation by DNA methylation is a potential non-invasive biomarker of gastric cancer. RPRML expression was evaluated by immunohistochemistry in 90 patients with gastric cancer and associated with clinicopathologic characteristics and outcomes. The role of RPRML in cancer biology was investigated in vitro, through RPRML ectopic overexpression. Functional experiments included colony formation, soft agar, MTS, and Ki67 immunofluorescence assays. DNA methylation-mediated silencing was evaluated by the 5-azacytidine assay and direct bisulfite sequencing. Non-invasive detection of circulating methylated RPRML DNA was assessed in 25 gastric cancer cases and 25 age- and sex-balanced cancer-free controls by the MethyLight assay. Downregulation of RPRML protein expression was associated with poor overall survival in advanced gastric cancer. RPRML overexpression significantly inhibited clonogenic capacity, anchorage-independent growth, and proliferation in vitro. Circulating methylated RPRML DNA distinguished patients with gastric cancer from controls with an area under the curve of 0.726. The in vitro overexpression results and the poor patient survival associated with lower RPRML levels suggest that RPRML plays a tumor-suppressive role in the stomach. Circulating methylated RPRML DNA may serve as a biomarker for the non-invasive detection of gastric cancer.

scholarly journals Circulating exosomal small RNAs are promising non‐invasive diagnostic biomarkers for gastric cancer

2020 ◽  
Vol 24 (24) ◽  
pp. 14502-14513 ◽  
Author(s):  
Lichen Ge ◽  
Nan Zhang ◽  
Dandan Li ◽  
Yingmin Wu ◽  
Hongsheng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Small Rnas ◽  
Diagnostic Biomarkers ◽  
Non Invasive

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.

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.

scholarly journals Aberrant methylation ofPCDH10andRASSF1Agenes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2112 ◽  
Author(s):  
Charinya Pimson ◽  
Tipaya Ekalaksananan ◽  
Chamsai Pientong ◽  
Supannee Promthet ◽  
Nuntiput Putthanachote ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Median Survival ◽  
Early Stage ◽  
Survival Rates ◽  
Aberrant Methylation ◽  
Blood Samples ◽  
Cumulative Survival ◽  
Non Invasive ◽  
Severe Stage

Background.Assessment of DNA methylation of specific genes is one approach to the diagnosis of cancer worldwide. Early stage detection is necessary to reduce the mortality rate of cancers, including those occurring in the stomach. For this purpose, tumor cells in circulating blood offer promising candidates for non-invasive diagnosis. Transcriptional inactivation of tumor suppressor genes, likePCDH10andRASSF1A, by methylation is associated with progression of gastric cancer, and such methylation can therefore be utilized as a biomarker.Methods.The present research was conducted to evaluate DNA methylation in these two genes using blood samples of gastric cancer cases. Clinicopathological data were also analyzed and cumulative survival rates generated for comparison.Results.High frequencies ofPCDH10andRASSF1Amethylations in the gastric cancer group were noted (94.1% and 83.2%, respectively, as compared to 2.97% and 5.45% in 202 matched controls). Most patients (53.4%) were in severe stage of the disease, with a median survival time of 8.4 months after diagnosis. Likewise, the patients with metastases, orRASSF1AandPCDH10methylations, had median survival times of 7.3, 7.8, and 8.4 months, respectively. A Kaplan–Meier analysis showed that cumulative survival was significantly lower in those cases positive for methylation ofRASSF1Athan in their negative counterparts. Similarly, whereas almost 100% of patients positive forPCDH10methylation had died after five years, none of the negative cases died over this period. Notably, the methylations ofRASSF1AandPCDH10were found to be higher in the late-stage patients and were also significantly correlated with metastasis and histology.Conclusions.PCDH10andRASSF1Amethylations in blood samples can serve as potential non-invasive diagnostic indicators in blood for gastric cancer. In addition toRASSF1Amethylation, tumor stage proved to be a major prognostic factor in terms of survival rates.

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%.

Prospective validation of a serum miRNA panel for early detection of gastric cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4065-4065 ◽  
Author(s):  
Lihan Zhou ◽  
Jimmy So ◽  
Ritika Kapoor ◽  
Feng Zhu ◽  
Ruiyang Zou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prospective Cohort ◽  
Histopathological Examination ◽  
Early Stage ◽  
Cost Effective ◽  
P Value ◽  
Diagnostic Endoscopy ◽  
Non Invasive ◽  
Serum Mirna ◽  
Multi Center Study

4065 Background: High mortality from gastric cancer is related to the late manifestation of its symptoms. A blood-based non-invasive biomarker with the ability to detect all stages of gastric cancer could significantly improve patient outcomes. We aimed to develop a novel serum miRNA assay for diagnosis of gastric cancer. Methods: We conducted a multi-center study involving 892 gastric cancer and control subjects from Singapore and Korea to develop a multi-target miRNA assay. Using RT-qPCR, we quantified the expressions of 578 serum miRNAs and constructed a 12-miR biomarker panel through multi-variant data analysis. The results were generated with the use of a logistic-regression algorithm, with the value of 40 or more considered to be positive. We subsequently validated this multi-miR assay in a large prospective cohort involving 4566 subjects and compared its performance with traditional markers such as H.Pylori and Pepsinogen. All participants underwent gastroscopy independent of the assay results. Results: Of the 4566 subjects that underwent gastroscopy and histopathological examination in the prospective cohort, 125 were diagnosed with gastric cancer. The 12-miR assay achieved an Area-Under-Curve (AUC) of 0.84, significantly outperforming (p-value < 0.01) that of H.Pylori (AUC of 0.64) and Pepsinogen (AUC of 0.62). The sensitivity of the miRNA assay in detecting early (stage 0-2) and late (stage 3-4) stage gastric cancer was 82.6% (95% CI, 68.6% to 92.2%) and 88.4% (95% CI, 78.4% to 94.9%) respectively at a specificity of 70.0% (95% CI, 67.8% to 71.9%). In comparison, H.Pylori showed a sensitivity of 80.4% at a specificity of 44.3% whereas the Pepsinogen showed sensitivity of 9.52% at a specificity of 95.3%. Using the miRNA assay as a pre-screening tool could potentially reduce number of endoscopy needed by 62% in detecting one case of gastric cancer. Conclusions: Our serum miRNA panel is a useful, non-invasive screening test for gastric cancer. It is cost-effective as it can reduce unnecessary diagnostic endoscopy.

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