Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients
Escuin i Borràs, Daniel (Institut de Recerca Sant Pau)
Bell, Olga (Institut de Recerca Sant Pau)
García-Valdecasas Vilanova, Bárbara (Institut de Recerca Sant Pau)
Clos Enríquez, Montserrat (Institut de Recerca Sant Pau)
Larrañaga, Itziar (Institut de Recerca Sant Pau)
López Vilaró, Laura (Institut de Recerca Sant Pau)
Mora, Josefina (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Andrés, Marta (Institut de Recerca Sant Pau)
Arqueros, Cristina (Institut de Recerca Sant Pau)
Barnadas i Molins, Agustí (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Deregulation of small non-coding RNAs (sncRNAs) has been associated with the onset of metastasis. We evaluated the expression of sncRNAs in patients with early-stage breast cancer, performing RNA sequencing in 60 patients for whom tumor and sentinel lymph node (SLN) samples were available, and conducting differential expression, gene ontology, enrichment and survival analyses. Sequencing annotation classified most of the sncRNAs into small nucleolar RNA (snoRNAs, 70%) and small nuclear RNA (snRNA, 13%). Our results showed no significant differences in sncRNA expression between tumor or SLNs obtained from the same patient. Differential expression analysis showed down-regulation (n = 21) sncRNAs and up-regulation (n = 2) sncRNAs in patients with locoregional metastasis. The expression of SNHG5, SNORD90, SCARNA2 and SNORD78 differentiated luminal A from luminal B tumors, whereas SNORD124 up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (SNORD93, SNORA16A, SNORD113-6, SNORA7A, SNORA57 and SNORA18A) that distinguished patients with locoregional metastasis and predicted patient outcome. Gene ontology and Reactome pathway analysis showed an enrichment of biological processes associated with translation initiation, protein targeting to specific cell locations, and positive regulation of Wnt and NOTCH signaling pathways, commonly involved in the promotion of metastases. Our results point to the potential of several sncRNAs as surrogate markers of lymph node metastases and patient outcome in early-stage breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant sncRNAs and to validate our results in a larger cohort of patients.
Grants:	Ministerio de Economía y Competitividad PI13/00110 Instituto de Salud Carlos III PI19/00362 Ministerio de Economía y Competitividad CB16/12/00471
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Biomarkers ; Early breast cancer ; Metastasis ; Sentinel lymph node ; Sncrnas ; Snornas
Published in:	International journal of molecular sciences, Vol. 25 (april 2024) , ISSN 1422-0067

DOI: 10.3390/ijms25073982
PMID: 38612790

15 p, 5.7 MB

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Articles > Research articles
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