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    Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
    (MDPI AG, 2025-04-03)
    María José Maturana
    ;
    Oslando Padilla
    ;
    Pablo M. Santoro
    ;
    Maria Alejandra Alarcón
    ;
    Wilda Olivares
    Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
      1Scopus© Citations 4
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    Cáncer de vesícula: ¿Es momento de modificar el GES?
    (SciELO Agencia Nacional de Investigacion y Desarrollo (ANID), 2024-10)
    Camila P. Samaniego
    ;
    Xabier de Aretxabala
    ;
    Felipe Castillo
    ;
    Álvaro Paredes
    ;
    M. Trinidad González
      14
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    Scopus© Citations 7  4
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    Quantifying regional variations in components of acute stroke unit (ASU) care in the international HeadPoST study
    (2020)
    Menglu Ouyang
    ;
    Yao Zhang
    ;
    Xia Wang
    ;
    Lili Song
    ;
    Laurent Billot
      1Scopus© Citations 6
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      2Scopus© Citations 4
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    Latin American consensus on uncomplicated recurrent urinary tract infection—2018
    (2019)
    Jorge Milhem Haddad
    ;
    Enrique Ubertazzi
    ;
    OSCAR ALFONSO STORME CABRERA
    ;
    Martha Medina
    ;
    Jorge Garcia
    Scopus© Citations 12  1
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    Circulating microparticles in cardiovascular disease: going on stage!
    (2019)
    Mauricio Fernández
    ;
    SEBASTIAN DANTE CALLIGARIS CAPRIOGLIO
      25Scopus© Citations 12
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    Síndrome Hemolítico Urémico asociado a Shigatoxina: ¿Cómo prevenirlo?
    (2019)
    CARLOS FELIPE GONZALO CAVAGNARO SANTA MARIA
    <jats:p>El síndrome hemolítico urémico (SHU) asociado a infección intestinal por bacterias productoras de Shigatoxina, que afecta principalmente a población infantil, puede causar morbilidad aguda grave, secuelas crónicas en varios órganos, y la muerte prematura en algunos de ellos. Dado su carácter zoonótico, adecuadas medidas de manejo agropecuario y correcta higiene de lo que consumimos es indispensable a la hora de prevenir la infección. Actualmente, una vez gatillado el SHU el manejo es médico y, principalmente, de soporte. En los últimos años diversas estrategias terapéuticas se han ido desarrollando para evitar que esta enfermedad ocurra, o, al menos, que pueda ser atenuada en sus consecuencias de morbi-mortalidad. El presente artículo describe acciones específicas a diferentes niveles de prevención de esta patología.</jats:p>
      35Scopus© Citations 6
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      8Scopus© Citations 5
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      1Scopus© Citations 60  5