Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients.
Background PIWI-interacting RNAs (piRNAs) are germline-characteristic small noncoding RNAs whose reactivation has been recently observed during carcinogenesis because of the germline reactivation program, which can be considered a hallmark of cancer. We evaluated the prognostic impact of hsa_piR_004...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/226864 |
| Acceso en línea: | https://hdl.handle.net/2445/226864 |
| Access Level: | acceso abierto |
| Palabra clave: | Oncogens Cèl·lules canceroses Càncer de pulmó Oncogenes Cancer cells Lung cancer |
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Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients.He, YangyiAcosta Plasencia, MelissaSánchez Lorente, DavidViñolas Segarra, NúriaMartínez Hernández, DanielDíaz Sánchez, TaniaAltuna Coy, AntonioNa, RishaLiu, YiBoada, MarcGuirao Montes, ÀngelaMolins López-Rodó, LaureanoMarrades Sicart, Ramon Ma.Navarro Ponz, AlfonsOncogensCèl·lules cancerosesCàncer de pulmóOncogenesCancer cellsLung cancerBackground PIWI-interacting RNAs (piRNAs) are germline-characteristic small noncoding RNAs whose reactivation has been recently observed during carcinogenesis because of the germline reactivation program, which can be considered a hallmark of cancer. We evaluated the prognostic impact of hsa_piR_004530 reactivation in non-small cell lung cancer (NSCLC) and studied its functional role in cell lines and organoids. Methods A total of 243 NSCLC resected patients were analyzed. Hsa_piR_004530 expression was quantified in tumor (n = 243) and normal tissue (n = 31) using qRT-PCR. Tumor recurrence, disease-free survival (DFS), and overall survival (OS) were used as clinical endpoints in survival analysis. Cox regression models were generated, and decision curve analysis for assessment of clinical benefit on disease prognosis was used. The effect of hsa_piR_004530 overexpression was assessed in NSCLC cell lines by cell migration, invasion, proliferation, apoptosis, and colony formation analysis. Patient-derived organoids from SCC patients were generated, and cell viability was evaluated after piRNA overexpression. Results Hsa_piR_004530 became reactivated on the tumor compared to normal tissue and was overexpressed in SCC patients. The prognosis analysis in the whole cohort showed that patients with high levels of hsa_piR_004530 had shorter DFS and OS. However, the subanalysis by histology revealed that the true prognostic impact of hsa_piR_004530 was specifically on SCC patients. These results became validated in an additional cohort. SCC patients with high hsa_piR_004530 had a higher relapse rate and shorter DFS and OS. Hsa_piR_004530 emerged as an independent prognostic factor in the multivariate analysis. Since the SCC patients who received adjuvant treatment had the best postsurgical prognosis, we focused on the role of hsa_piR_004530 on non-treated patients, which allowed us to identify a high-risk group where the piRNA ameliorated patients’ risk stratification, highlighting superior clinical benefit in postsurgical relapse prediction. Hsa_piR_004530 overexpression was associated with increased migration, invasion, and colony formation. Moreover, the overexpression induced stem cell gene activation and correlated with higher size spheroid formation. In patient-derived organoids, the overexpression boosted organoid cell viability. Conclusions Hsa_piR_004530 became reactivated in NSCLC, where it played a role as an oncogene, and its higher levels correlated with disease recurrence and shorter survival in SCC patients.BioMed Central2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/226864Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12916-025-04342-1BMC Medicine, 2025, vol. 23, num.1https://doi.org/10.1186/s12916-025-04342-1cc-by-nc-nd (c) He, Y. et al., 2025http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2268642026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| title |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| spellingShingle |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. He, Yangyi Oncogens Cèl·lules canceroses Càncer de pulmó Oncogenes Cancer cells Lung cancer |
| title_short |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| title_full |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| title_fullStr |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| title_full_unstemmed |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| title_sort |
Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients. |
| dc.creator.none.fl_str_mv |
He, Yangyi Acosta Plasencia, Melissa Sánchez Lorente, David Viñolas Segarra, Núria Martínez Hernández, Daniel Díaz Sánchez, Tania Altuna Coy, Antonio Na, Risha Liu, Yi Boada, Marc Guirao Montes, Àngela Molins López-Rodó, Laureano Marrades Sicart, Ramon Ma. Navarro Ponz, Alfons |
| author |
He, Yangyi |
| author_facet |
He, Yangyi Acosta Plasencia, Melissa Sánchez Lorente, David Viñolas Segarra, Núria Martínez Hernández, Daniel Díaz Sánchez, Tania Altuna Coy, Antonio Na, Risha Liu, Yi Boada, Marc Guirao Montes, Àngela Molins López-Rodó, Laureano Marrades Sicart, Ramon Ma. Navarro Ponz, Alfons |
| author_role |
author |
| author2 |
Acosta Plasencia, Melissa Sánchez Lorente, David Viñolas Segarra, Núria Martínez Hernández, Daniel Díaz Sánchez, Tania Altuna Coy, Antonio Na, Risha Liu, Yi Boada, Marc Guirao Montes, Àngela Molins López-Rodó, Laureano Marrades Sicart, Ramon Ma. Navarro Ponz, Alfons |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Oncogens Cèl·lules canceroses Càncer de pulmó Oncogenes Cancer cells Lung cancer |
| topic |
Oncogens Cèl·lules canceroses Càncer de pulmó Oncogenes Cancer cells Lung cancer |
| description |
Background PIWI-interacting RNAs (piRNAs) are germline-characteristic small noncoding RNAs whose reactivation has been recently observed during carcinogenesis because of the germline reactivation program, which can be considered a hallmark of cancer. We evaluated the prognostic impact of hsa_piR_004530 reactivation in non-small cell lung cancer (NSCLC) and studied its functional role in cell lines and organoids. Methods A total of 243 NSCLC resected patients were analyzed. Hsa_piR_004530 expression was quantified in tumor (n = 243) and normal tissue (n = 31) using qRT-PCR. Tumor recurrence, disease-free survival (DFS), and overall survival (OS) were used as clinical endpoints in survival analysis. Cox regression models were generated, and decision curve analysis for assessment of clinical benefit on disease prognosis was used. The effect of hsa_piR_004530 overexpression was assessed in NSCLC cell lines by cell migration, invasion, proliferation, apoptosis, and colony formation analysis. Patient-derived organoids from SCC patients were generated, and cell viability was evaluated after piRNA overexpression. Results Hsa_piR_004530 became reactivated on the tumor compared to normal tissue and was overexpressed in SCC patients. The prognosis analysis in the whole cohort showed that patients with high levels of hsa_piR_004530 had shorter DFS and OS. However, the subanalysis by histology revealed that the true prognostic impact of hsa_piR_004530 was specifically on SCC patients. These results became validated in an additional cohort. SCC patients with high hsa_piR_004530 had a higher relapse rate and shorter DFS and OS. Hsa_piR_004530 emerged as an independent prognostic factor in the multivariate analysis. Since the SCC patients who received adjuvant treatment had the best postsurgical prognosis, we focused on the role of hsa_piR_004530 on non-treated patients, which allowed us to identify a high-risk group where the piRNA ameliorated patients’ risk stratification, highlighting superior clinical benefit in postsurgical relapse prediction. Hsa_piR_004530 overexpression was associated with increased migration, invasion, and colony formation. Moreover, the overexpression induced stem cell gene activation and correlated with higher size spheroid formation. In patient-derived organoids, the overexpression boosted organoid cell viability. Conclusions Hsa_piR_004530 became reactivated in NSCLC, where it played a role as an oncogene, and its higher levels correlated with disease recurrence and shorter survival in SCC patients. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/226864 |
| url |
https://hdl.handle.net/2445/226864 |
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Inglés |
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Inglés |
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Reproducció del document publicat a: https://doi.org/10.1186/s12916-025-04342-1 BMC Medicine, 2025, vol. 23, num.1 https://doi.org/10.1186/s12916-025-04342-1 |
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cc-by-nc-nd (c) He, Y. et al., 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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cc-by-nc-nd (c) He, Y. et al., 2025 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
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BioMed Central |
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BioMed Central |
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Articles publicats en revistes (Medicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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