Role of Reprimo-like as a a tumor suppressor and candidate biomarker in gastric cancer

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dc.contributor.advisorCorvalán R., Alejandro
dc.contributor.authorAlarcón Alarcón, María Alejandra
dc.contributor.otherPontificia Universidad Católica de Chile. Facultad de Medicina
dc.date2020-10-22
dc.date.accessioned2020-10-23T16:22:23Z
dc.date.issued2020
dc.date.updated2020-10-20T17:27:03Z
dc.descriptionTesis (Doctor of Philosophy in Medical Sciences)--Pontificia Universidad Católica de Chile, 2020
dc.description.abstractReprimo-like (RPRML) is an uncharacterized member of the Reprimo gene family. Herein, 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 outcome. 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 64 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 discriminated patients with gastric cancer from controls with an area under the curve of 0.729. 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.
dc.description.version2020-10-22
dc.format.extent57 páginas
dc.identifier.doi10.7764/tesisUC/MED/48099
dc.identifier.urihttps://doi.org/10.7764/tesisUC/MED/48099
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/48099
dc.language.isoen
dc.nota.accesoContenido completo
dc.rightsacceso abierto
dc.subject.ddc616.99433
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherCáncer gástrico - Genéticaes_ES
dc.subject.otherMarcadores genéticoses_ES
dc.titleRole of Reprimo-like as a a tumor suppressor and candidate biomarker in gastric canceres_ES
dc.typetesis doctoral
sipa.codpersvinculados63885
sipa.codpersvinculados155072
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