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Background <p>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.</p> Methods <p>A total of 243 NSCLC resected patients were analyzed. Hsa_piR_004530 expression was quantified in tumor (<i>n</i> = 243) and normal tissue (<i>n</i> = 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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Impact of piR_004530 reactivation in lung cancer: implications for recurrence and survival of lung squamous cell carcinoma patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月7日

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  • Yangyi He,
  • Melissa Acosta-Plasencia,
  • David Sánchez-Lorente,
  • Nuria Viñolas,
  • Daniel Martinez,
  • Tania Díaz,
  • Antonio Altuna-Coy,
  • Risha Na,
  • Yi Liu,
  • Marc Boada,
  • Angela Guirao,
  • Laureano Molins,
  • Ramón M. Marrades,
  • Alfons Navarro

摘要

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.