Methylation status and long‐fragment cell‐free DNA are prognostic biomarkers for gastric cancer

Epigenetic modification of several genes is a key component in the development of gastric cancer. The methylation status of RASSF1A, SOX17 and Wif-1 genes was evaluated in the cell free circulating DNA of 70 patients with advanced gastric cancer, using methylation-specific PCR. Patients with higher cell-free DNA concentration seem to have lower PFS, than patients with lower cell-free DNA concentration (p = 0.001). RASSF1A was the tumor suppressor gene, most frequently methylated in metastatic gastric cancer patients, followed by SOX17 and Wif-1 (74.3%, 60.0% and 47.1%, respectively). Patients having the SOX17 promoter methylated, had lower progression free survival and overall survival, than unmethylated ones (p < 0.001). Patients having the Wif-1 promoter methylated, had lower progression free survival and overall survival, than unmethylated ones (p = 0.001). Patients having the RASSF1A promoter methylated, had lower progression free survival and overall survival, than unmethylated ones (p = 0.004). Promoter methylation of the examined genes was significantly associated with a decrease in progression free survival and overall survival, comparing to that of patients without methylation. Simultaneous methylation of the above genes was associated with even worse progression free survival and overall survival. The methylation of RASSF1A, SOX-17 and Wif-1 and genes, is a frequent epigenetic event in patients with advanced gastric cancer.

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Methylation of FBN1, SPG20, ITF2, RUNX3, SNCA, MLH1, and SEPT9 genes in circulating cell-free DNA as biomarkers of colorectal cancer

Cancer Biomarkers ◽

10.3233/cbm-210315 ◽

2021 ◽

pp. 1-30

Author(s):

Maryam Alizadeh-Sedigh ◽

Mohammad Sadegh Fazeli ◽

Habibollah Mahmoodzadeh ◽

Shahin Behrouz Sharif ◽

Ladan Teimoori-Toolabi

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Diagnostic Performance ◽

Methylation Status ◽

Melting Curve ◽

Melting Curve Analysis ◽

Promoter Regions ◽

Cell Free Dna ◽

Free Dna ◽

Tumor Tissues

BACKGROUND: Investigating aberrant tumor-specific methylation in plasma cell-free DNA provides a promising and noninvasive biomarker for cancer detection. OBJECTIVE: We aimed to investigate methylation status of some promoter regions in the plasma and tumor tissues to find biomarkers for early detection of colorectal cancer. METHODS: This case-control study on seventy colorectal cancer patients and fifty matched healthy controls used Methylation-Specific High-Resolution Melting Curve analysis to evaluate the methylation of the selected promoter regions in converted genomic tissue DNA and plasma cfDNA. RESULTS: The methylation levels in selected regions of SPG20 (+24375 to +24680, +24209 to +24399, and +23625 to +23883), SNCA (+807 to +1013, +7 to +162, and -180 to +7), FBN1 (+223 to +429, +1 to +245, and -18 to -175), ITF2 (+296 to +436 and -180 to +55), SEPT9 (-914412 to -91590 and -99083 to -92264), and MLH1 (-13 to +22) were significantly higher in tumor tissues compared with normal adjacent tissues. The methylation levels of FBN1, ITF2, SNCA, and SPG20 promoters were significantly higher in the patient’s plasma compared to patient’s normal tissue and plasma of healthy control subjects. FBN1, SPG20, and SEPT9 promoter methylation had a good diagnostic performance for discriminating CRC tissues from normal adjacent tissues (AUC > 0.8). A panel of SPG20, FBN1, and SEPT9 methylation had a higher diagnostic value than that of any single biomarker and other panels in tissue-based assay (AUC > 0.9). The methylation of FBN1(a) and SPG20(a) regions, as the closest region to the first coding sequence (CDS), had a good diagnostic performance in plasma cfDNA (AUC > 0.8) while a panel consisted of FBN1(a) and SPG20(a) regions showed excellent diagnostic performance for CRC detection in plasma cfDNA (AUC > 0.9). CONCLUSION: Methylation of FBN1(a) and SPG20(a) promoter regions in the plasma cfDNA can be an excellent simple, non-invasive blood-based test for early detection of CRC.

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Prediction of cancer progression in a group of 73 gastric cancer patients by circulating cell-free DNA

BMC Cancer ◽

10.1186/s12885-016-2977-7 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 11

Author(s):

Wang-Yang Pu ◽

Rong Zhang ◽

Li Xiao ◽

Yong-You Wu ◽

Wei Gong ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Cell Free Dna ◽

Free Dna ◽

Gastric Cancer Patients ◽

Circulating Cell Free Dna

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Screening for Colorectal Cancer Based on the Promoter Methylation Status of the Septin 9 Gene in Plasma Cell Free DNA

Journal of Clinical Epigenetics ◽

10.21767/2472-1158.100040 ◽

2017 ◽

Vol 03 (01) ◽

Cited By ~ 4

Author(s):

Theo deVos ◽

Bela Molnar

Keyword(s):

Colorectal Cancer ◽

Plasma Cell ◽

Promoter Methylation ◽

Methylation Status ◽

Cell Free Dna ◽

Promoter Methylation Status ◽

Septin 9 ◽

Free Dna

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Methylation Status of Immune Response Genes Promoters in Cell-Free DNA Differs in Hemodialyzed Patients with Diabetic Nephropathy According to the Intensity of Anemia Therapy

Blood Purification ◽

10.1159/000356094 ◽

2013 ◽

Vol 36 (3-4) ◽

pp. 280-286 ◽

Cited By ~ 4

Author(s):

Marie Korabecna ◽

Eva Pazourkova ◽

Ales Horinek ◽

Magdalena Mokrejsova ◽

Vladimir Tesar

Keyword(s):

Immune Response ◽

Diabetic Nephropathy ◽

Methylation Status ◽

Cell Free Dna ◽

Immune Response Genes ◽

Free Dna

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

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.27 ◽

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%.

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