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.

scholarly journals Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Biyuan Luo ◽  
Fang Ma ◽  
Hao Liu ◽  
Jixiong Hu ◽  
Le Rao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
High Risk ◽  
Validation Cohort ◽  
Early Stage ◽  
High Risk Population ◽  
Risk Population ◽  
Tissue Samples ◽  
Non Invasive ◽  
Independent Validation ◽  
Screening Model

Abstract Background Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). Methods Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. Results Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939–0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758–0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905–0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml−1) from high risk population (AUC=0.93; 95% CI 0.892–0.969). Conclusions We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. Trial registration The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(#NCT04383353).

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.

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.

Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1036-1039 ◽  
Author(s):  
J J Grau ◽  
J Estapé ◽  
J Fuster ◽  
X Filella ◽  
J Visa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Survival Rates ◽  
Group Versus ◽  
Node Negative ◽  
Treatment Groups ◽  
Locally Advanced Gastric Cancer

PURPOSE We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

Use of perioperative therapy in gastric cancer: A retrospective comparison of ECF and chemoradiation.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 112-112
Author(s):  
V. Siripurapu ◽  
J. C. Watson ◽  
J. P. Hoffman
Keyword(s):  
Gastric Cancer ◽  
Median Survival ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Preoperative Treatment ◽  
Perioperative Therapy ◽  
Significant Group ◽  
Group 2 ◽  
Group 1

112 Background: Gastric Cancer (GC) remains a major cause of cancer related morbidity and mortality in Western Countries with five year survival rates between 30%-40%. Preoperative therapy has been championed by groups extrapolating data from the Intergroup 0116 and the MAGIC trials, with a view to enhancing completion of therapy and improving survival in locally advanced tumors. Methods: Patients with preoperative treatment of GC were reviewed from our tumor registry. Stages were assigned by AJCC 7th edition. A comparison between the ECF regimen and non-ECF chemoradiation regimens was performed to view patterns of pathologic complete response (pCR), recurrence, toxicity and overall survival. Results: Forty-two patients were identified and stratified into two groups; Group 1 ECF treatment arm (n = 16) compared to group 2 non-ECF chemo-radiation arm (n = 26). No statistical difference was noted in age, ethnicity or stage stratification. All of Group 1 received their chemotherapy regimen after 2005. In contrast, 60% of Group 2 patients received their treatment pre-2005. Only 56% the ECF group completed their treatment course (19% received other postoperative therapy). Seventy percent of group 2 received adjuvant chemotherapy. A grade 2 or higher toxicity was noted in 16% of Group 1 compared to 60% in Group 2 (p = 0.035). Seven complications were noted in the group 1 compared to 10 in group 2 (p = NS). The differentiation of tumor between groups was not significant (p = 0.97). Length of stay was significant (Group 1:9 days, Group 2:12 days, p = 0.02). More nodes were retrieved from group 1 versus group 2 (20.2 versus 15.2, p = 0.03). Group 1 had 3 recurrences (19%) while Group 2 had 11 recurrences (42%, p = 0.94). In both groups 80% of recurrences were distant. Group 1 had a 19% pCR versus 23% in group 2 (p = 0.79). Two-year survival was 70% in both groups, with a median survival of 51 months for group 2. Median survival was not reached for group 1. Conclusions: No difference was noted in pCR, recurrences, or survival between these two regimens. If this can be confirmed in larger, prospective, randomized trials, use of radiation and its potential morbidity may be avoided. No significant financial relationships to disclose.

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.

scholarly journals Diagnostic classification based on DNA methylation profiles using sequential machine learning approaches

2021 ◽  
Author(s):  
M. W. Wojewodzic ◽  
J. P. Lavender
Keyword(s):  
Machine Learning ◽  
Dna Methylation ◽  
Machine Learning Algorithms ◽  
Aberrant Methylation ◽  
Learning Approaches ◽  
Tissue Samples ◽  
Non Invasive ◽  
Genome Wide ◽  
Cancer Types ◽  
Methylation Patterns

AbstractAberrant methylation patterns in human DNA have great potential for the discovery of novel diagnostic and disease progression biomarkers. In this paper, we used machine learning algorithms to identify promising methylation sites for diagnosing cancerous tissue and to classify patients based on methylation values at these sites.We used genome-wide DNA methylation patterns from both cancerous and normal tissue samples, obtained from the Genomic Data Commons consortium and trialled our methods on three types of urological cancer. A decision tree was used to identify the methylation sites most useful for diagnosis.The identified locations were then used to train a neural network to classify samples as either cancerous or non-cancerous. Using this two-step approach we found strong indicative biomarker panels for each of the three cancer types.These methods could likely be translated to other cancers and improved by using non-invasive liquid methods such as blood instead of biopsy tissue.

scholarly journals Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chi T. Viet ◽  
Xinyu Zhang ◽  
Ke Xu ◽  
Gary Yu ◽  
Kesava Asam ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Oral Cancer ◽  
Association Studies ◽  
Survival Rates ◽  
Methylation Array ◽  
Tissue Samples ◽  
Dna Yield ◽  
Normal Tissues ◽  
Non Invasive ◽  
Clinical Biomarker

Abstract Background Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. Methods Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. Results There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). Conclusions Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

scholarly journals Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5992
Author(s):  
Francesco Greco ◽  
Federica Anastasi ◽  
Luca Fidia Pardini ◽  
Marialaura Dilillo ◽  
Eleonora Vannini ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Extracellular Vesicles ◽  
Murine Model ◽  
Biomarker Discovery ◽  
Early Stage ◽  
Protein Profile ◽  
Survival Rates ◽  
Non Invasive ◽  
Tumor Stages ◽  
Early Effects

Glioblastoma Multiforme (GBM) is a brain tumor with a poor prognosis and low survival rates. GBM is diagnosed at an advanced stage, so little information is available on the early stage of the disease and few improvements have been made for earlier diagnosis. Longitudinal murine models are a promising platform for biomarker discovery as they allow access to the early stages of the disease. Nevertheless, their use in proteomics has been limited owing to the low sample amount that can be collected at each longitudinal time point. Here we used optimized microproteomics workflows to investigate longitudinal changes in the protein profile of serum, serum small extracellular vesicles (sEVs), and cerebrospinal fluid (CSF) in a GBM murine model. Baseline, pre-symptomatic, and symptomatic tumor stages were determined using non-invasive motor tests. Forty-four proteins displayed significant differences in signal intensities during GBM progression. Dysregulated proteins are involved in cell motility, cell growth, and angiogenesis. Most of the dysregulated proteins already exhibited a difference from baseline at the pre-symptomatic stage of the disease, suggesting that early effects of GBM might be detectable before symptom onset.

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