Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
Abstract
:1. Introduction
2. Results
2.1. RPRM Promoter Methylation in Gastric Cancer Tissues
2.2. RPRM Promoter Methylation in Paired Tissue and Plasma Gastric Cancer Samples
2.3. Characterization of Methylated RPRM Cell-Free DNA as a Biomarker for Non-Invasive Detection of Gastric Cancer (Cohort 1)
2.4. Characterization of Methylated RPRM Cell-Free DNA as a Biomarker for Monitoring Gastric Cancer Treatment Response (Cohort 2)
2.5. Evaluation of Methylated RPRM Cell-Free DNA Across the Premalignant Conditions and Gastric Cancer (Cohort 3)
3. Discussion
4. Methods
4.1. Clinical Samples
4.2. Molecular Biology Methods
4.3. Enzyme-Linked Immunosorbent Assay (ELISA) Method for the Detection of PG and H. pylori
4.4. Biostatistical Methods
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Statistic | Value | 95% CI |
---|---|---|
Sensitivity | 65.00% | 53.52% to 75.33% |
Specificity | 75.90% | 73.16% to 78.49% |
Positive Likelihood Ratio | 2.70 | 2.22 to 3.28 |
Negative Likelihood Ratio | 0.46 | 0.34 to 0.62 |
Disease prevalence | 7.24% | 5.78% to 8.93% |
Positive Predictive Value | 17.39% | 14.78% to 20.36% |
Negative Predictive Value | 96.53% | 95.36% to 97.40% |
Accuracy | 75.11% | 72.45% to 77.64% |
Non-Adjusted | Adjusted by Sex and Age | ||||||
---|---|---|---|---|---|---|---|
Lesion Grade | Positive n (%) | Odds Ratio (Crude Rate) | 95% C.I. OR | p-Value | Odds Ratio (Adjusted) | 95% C.I. OR | p-Value |
Normal (No histological analysis was performed) | 34 (18.89) | reference | reference | reference | reference | reference | reference |
Chronic atrophic gastritis | 167 (24.13) | 1.37 | 0.91 to 2.06 | 0.164 | 1.37 | 0.90 to 2.07 | 0.140 |
Intestinal metaplasia and low grade dysplasia | 46 (30.07) | 1.85 | 1.11 to 3.07 | 0.020 | 1.60 | 0.93 to 2.75 | 0.091 |
Early gastric cancer (stage I-II) and high-grade dysplasia | 10 (47.62) | 3.90 | 1.53 to 9.94 | 0.004 | 3.23 | 1.15 to 9.11 | 0.026 |
Advanced gastric cancer (stage III-IV) | 42 (71.19) | 10.61 | 5.40 to 20.85 | <0.0001 | 9.79 | 4.43 to 21.61 | <0.0001 |
Chronic atrophic gastritis and gastric intestinal metaplasia/low-grade dysplasia | 213 (25.21) | 1.45 | 0.97 to 2.17 | 0.084 | 1.40 | 0.93 to 2.11 | 0.104 |
Early gastric cancer (stage I-II)/high-grade dysplasia and advanced gastric cancer | 52 (65.00) | 7.98 | 4.41 to 14.41 | <0.0001 | 6.93 | 3.48 to 13.81 | <0.0001 |
Test | Cases | Controls | Sensitivity | Specificity | Odds Ratio | ||||
---|---|---|---|---|---|---|---|---|---|
n = 19 | n = 92 | % | 95% CI | % | 95% CI | Odds Ratio | 95% CI | p-Value | |
Methylated RPRM cfDNA | 47.37% | 24.45% to 71.14% | 77.17% | 67.25% to 85.28% | 3.04 | 1.09 to 8.47 | 0.033 | ||
positive | 9 | 21 | |||||||
negative | 10 | 71 | |||||||
PG-I/II ratio | 52.63% | 28.86% to 75.55% | 80.22% | 70.55% to 87.84% | 4.51 | 1.60 to 12.72 | 0.005 | ||
Positive | 10 | 18 | |||||||
Negative | 9 | 74 | |||||||
Combined Methylated RPRM cfDNA or PG-I/II ratio | 78.95% | 54.43% to 93.95% | 63.04% | 52.34% to 72.88% | 6.40 | 1.96 to 20.85 | 0.002 | ||
Positive | 15 | 34 | |||||||
Negative | 4 | 58 |
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Maturana, M.J.; Padilla, O.; Santoro, P.M.; Alarcón, M.A.; Olivares, W.; Blanco, A.; Armisen, R.; Garrido, M.; Aravena, E.; Barrientos, C.; et al. Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer. Int. J. Mol. Sci. 2025, 26, 3333. https://doi.org/10.3390/ijms26073333
Maturana MJ, Padilla O, Santoro PM, Alarcón MA, Olivares W, Blanco A, Armisen R, Garrido M, Aravena E, Barrientos C, et al. Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer. International Journal of Molecular Sciences. 2025; 26(7):3333. https://doi.org/10.3390/ijms26073333
Chicago/Turabian StyleMaturana, María José, Oslando Padilla, Pablo M. Santoro, Maria Alejandra Alarcón, Wilda Olivares, Alejandro Blanco, Ricardo Armisen, Marcelo Garrido, Edmundo Aravena, Carlos Barrientos, and et al. 2025. "Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer" International Journal of Molecular Sciences 26, no. 7: 3333. https://doi.org/10.3390/ijms26073333
APA StyleMaturana, M. J., Padilla, O., Santoro, P. M., Alarcón, M. A., Olivares, W., Blanco, A., Armisen, R., Garrido, M., Aravena, E., Barrientos, C., Calvo-Belmar, A., & Corvalán, A. H. (2025). Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer. International Journal of Molecular Sciences, 26(7), 3333. https://doi.org/10.3390/ijms26073333