Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients
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 condu...
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3982 |
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| author | Daniel Escuin Olga Bell Bárbara García-Valdecasas Montserrat Clos Itziar Larrañaga Laura López-Vilaró Josefina Mora Marta Andrés Cristina Arqueros Agustí Barnadas |
| author_facet | Daniel Escuin Olga Bell Bárbara García-Valdecasas Montserrat Clos Itziar Larrañaga Laura López-Vilaró Josefina Mora Marta Andrés Cristina Arqueros Agustí Barnadas |
| author_sort | Daniel Escuin |
| collection | DOAJ |
| description | 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 <i>SNHG5</i>, <i>SNORD90</i>, <i>SCARNA2</i> and <i>SNORD78</i> differentiated luminal A from luminal B tumors, whereas <i>SNORD124</i> up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (<i>SNORD93</i>, <i>SNORA16A</i>, <i>SNORD113-6</i>, <i>SNORA7A</i>, <i>SNORA57</i> and <i>SNORA18A</i>) 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. |
| first_indexed | 2024-04-24T10:41:52Z |
| format | Article |
| id | doaj.art-085f7fad99dc46d98e56461e12cd9788 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:41:52Z |
| publishDate | 2024-04-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-085f7fad99dc46d98e56461e12cd97882024-04-12T13:20:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257398210.3390/ijms25073982Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer PatientsDaniel Escuin0Olga Bell1Bárbara García-Valdecasas2Montserrat Clos3Itziar Larrañaga4Laura López-Vilaró5Josefina Mora6Marta Andrés7Cristina Arqueros8Agustí Barnadas9Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainHospital de la Santa Creu i Sant Pau, 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainInstitut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, SpainDeregulation 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 <i>SNHG5</i>, <i>SNORD90</i>, <i>SCARNA2</i> and <i>SNORD78</i> differentiated luminal A from luminal B tumors, whereas <i>SNORD124</i> up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (<i>SNORD93</i>, <i>SNORA16A</i>, <i>SNORD113-6</i>, <i>SNORA7A</i>, <i>SNORA57</i> and <i>SNORA18A</i>) 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.https://www.mdpi.com/1422-0067/25/7/3982sncRNAssnoRNAsearly breast cancersentinel lymph nodemetastasisbiomarkers |
| spellingShingle | Daniel Escuin Olga Bell Bárbara García-Valdecasas Montserrat Clos Itziar Larrañaga Laura López-Vilaró Josefina Mora Marta Andrés Cristina Arqueros Agustí Barnadas Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients International Journal of Molecular Sciences sncRNAs snoRNAs early breast cancer sentinel lymph node metastasis biomarkers |
| title | Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients |
| title_full | Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients |
| title_fullStr | Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients |
| title_full_unstemmed | Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients |
| title_short | Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients |
| title_sort | small non coding rnas and their role in locoregional metastasis and outcomes in early stage breast cancer patients |
| topic | sncRNAs snoRNAs early breast cancer sentinel lymph node metastasis biomarkers |
| url | https://www.mdpi.com/1422-0067/25/7/3982 |
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