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Article

Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients

by
Daniel Escuin
1,*,
Olga Bell
1,
Bárbara García-Valdecasas
1,2,
Montserrat Clos
1,2,
Itziar Larrañaga
1,2,
Laura López-Vilaró
1,2,
Josefina Mora
2,
Marta Andrés
1,2,
Cristina Arqueros
1,2 and
Agustí Barnadas
1,2,3,4
1
Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain
2
Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
3
School of Medicine, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain
4
Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(7), 3982; https://doi.org/10.3390/ijms25073982
Submission received: 1 March 2024 / Revised: 18 March 2024 / Accepted: 27 March 2024 / Published: 3 April 2024
(This article belongs to the Special Issue Non-coding RNA (ncRNA) in Cancer : 2nd Edition)
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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.
Keywords: sncRNAs; snoRNAs; early breast cancer; sentinel lymph node; metastasis; biomarkers sncRNAs; snoRNAs; early breast cancer; sentinel lymph node; metastasis; biomarkers

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MDPI and ACS Style

Escuin, D.; Bell, O.; García-Valdecasas, B.; Clos, M.; Larrañaga, I.; López-Vilaró, L.; Mora, J.; Andrés, M.; Arqueros, C.; Barnadas, A. Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients. Int. J. Mol. Sci. 2024, 25, 3982. https://doi.org/10.3390/ijms25073982

AMA Style

Escuin D, Bell O, García-Valdecasas B, Clos M, Larrañaga I, López-Vilaró L, Mora J, Andrés M, Arqueros C, Barnadas A. Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients. International Journal of Molecular Sciences. 2024; 25(7):3982. https://doi.org/10.3390/ijms25073982

Chicago/Turabian Style

Escuin, Daniel, Olga Bell, Bárbara García-Valdecasas, Montserrat Clos, Itziar Larrañaga, Laura López-Vilaró, Josefina Mora, Marta Andrés, Cristina Arqueros, and Agustí Barnadas. 2024. "Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients" International Journal of Molecular Sciences 25, no. 7: 3982. https://doi.org/10.3390/ijms25073982

APA Style

Escuin, D., Bell, O., García-Valdecasas, B., Clos, M., Larrañaga, I., López-Vilaró, L., Mora, J., Andrés, M., Arqueros, C., & Barnadas, A. (2024). Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients. International Journal of Molecular Sciences, 25(7), 3982. https://doi.org/10.3390/ijms25073982

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