Portal de investigación
Baseline extracellular vesicle miRNA-30c and autophagic CTCs predict chemoradiotherapy resistance and outcomes in patients with lung cancer
Fecha de publicación:
Fecha Ahead of Print:
Autores organización
Autores
- de Miguel-Perez D
- Ortega FG
- Tejada RG
- Martínez-Única A
- Peterson CB
- Russo A
- Gunasekaran M
- Amezcua V
- Lorente JA
- Expósito Hernández J
- Rolfo C
- Serrano MJ
Grupos de investigación
Resumen
Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 patients with stage III NSCLC undergoing cCRT. Our findings revealed that non-responders exhibited low levels of baseline EV miR-375, miR-200c, and miR-30c. In particular, EV miR-30c showed high predictive value with an area under the curve of 87.2%. Low EV miR-30c and the presence of autophagic-activated CTCs emerged as independent predictive biomarkers for shorter relapse-free survival and overall survival. Furthermore, in experimental models simulating the effects of chemo- and radiotherapy, the administration of miR-30c, either through direct transfection or encapsulation into human EVs, led to the inhibition of autophagy in these cells. This is the first report demonstrating that EV miR-30c inhibits tumor autophagy and its quantification, together with autophagic-activated CTCs, could be used as biomarkers for the stratification and monitoring of patients with NSCLC undergoing cCRT, and they may hold promising potential for guiding subsequent consolidation treatment with immunotherapy or other novel therapies based on autophagy inhibitors. © 2023, The Author(s).
© 2023. The Author(s).
Datos de la publicación
- ISSN/ISSNe:
- 2050-7771, 2050-7771
- Tipo:
- Letter
- Páginas:
- 98-98
- Enlace a otro recurso:
- www.scopus.com
Biomarker Research BioMed Central Ltd
Citas Recibidas en Scopus: 9
Documentos
- No hay documentos
Filiaciones
Keywords
- biological marker; microRNA; microRNA 200c; microRNA 375; miRNA30c; tumor marker; unclassified drug; area under the curve; autophagy (cellular); cancer inhibition; cancer survival; cell differentiation; cell viability; chemoradiotherapy; circulating tumor cell; controlled study; encapsulation; exosome; gene expression; human; Letter; lung cancer; non small cell lung cancer; outcome assessment; overall survival; predictive value; receiver operating characteristic; recurrence free survival; sensitivity and specificity; survival analysis; transmission electron microscopy; Western blotting
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Citar la publicación
de Miguel D,Ortega FG,Tejada RG,Martínez A,Peterson CB,Russo A,Gunasekaran M,Cardona AF,Amezcua V,Lorente JA,Expósito J,Rolfo C,Serrano MJ. Baseline extracellular vesicle miRNA-30c and autophagic CTCs predict chemoradiotherapy resistance and outcomes in patients with lung cancer. Biomark Res. 2023. 11(1):p. 98-98. IF:9,500. (1).