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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224587
CircRNA and piRNAs as Biomarkers in Non-Small Cell Lung Cancer: Their Role in Tumor Progression and Patient Outcome
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[eng] Introduction: Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for 85% of cases. It is divided into pulmonary adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), which differ in their origin, progression, and response to treatment. Despite advances in surgery and therapies, postoperative recurrence remains a challenge that limits long-term survival. Non-coding RNAs (ncRNAs) have emerged as key regulators in tumor biology, affecting cell proliferation, apoptosis, and epigenetic remodeling. Within these, circular RNAs (circRNAs) and piwi-interacting RNAs (piRNAs) have been shown to play an important role in the regulation of cancer. Although they have been studied in NSCLC, the role of circRNAs and piRNAs in postoperative recurrence is still unclear. Given that NSCLC subtypes present molecular differences and respond heterogeneously to treatments, it is essential to identify new biomarkers that allow the risk of recurrence to be stratified and personalized therapeutic strategies to be designed. Hypothesis: ncRNAs, specifically circRNAs and piRNAs, specifically regulate tumor progression in the different subtypes of NSCLC, influencing postoperative recurrence through epigenetic mechanisms and interaction with the PIWI/piRNA pathway. Their study can establish new prognostic biomarkers and contribute to the development of personalized models for predicting recurrence. Main objective: To evaluate the role of circRNA-10720 and piRNAs hsa_piR_004530, hsa_piR_022710, hsa_piR_019822 and hsa_piR_020840 in NSCLC recurrence, exploring their potential as prognostic biomarkers and their involvement in tumor progression. In addition, the function of these piRNAs in different subtypes of NSCLC will be specifically analyzed, considering their molecular and clinical differences. Specific objectives • To determine the differential expression of circRNA-10720 and selected piRNAs in tumor and normal tissues of patients with resected NSCLC, correlating it with clinical and pathological characteristics. • To evaluate its prognostic value in predicting postoperative recurrence and its impact on disease-free survival and overall survival. • To explore the molecular and epigenetic mechanisms by which these ncRNAs regulate tumor progression and the possible application of these in the stratification of the risk of recurrence in different subtypes of NSCLC. • To investigate their functional roles in cell models of NSCLC, analysing their impact on proliferation, migration, invasion and regulation of epithelial-mesenchymal transition (EMT). Methods: To evaluate the expression and functional impact of circRNA-10720 and piRNAs hsa_piR_004530, hsa_piR_022710, hsa_piR_019822 and hsa_piR_020840 on NSCLC recurrence, paired tumor and normal tissue samples were collected from patients with resected NSCLC, and the expression of these ncRNAs was quantified by RT-qPCR in an independent cohort. Subsequently, the relationship between expression levels and clinical-pathological parameters, including tumor stage, histological grade and postoperative recurrence, was analyzed, evaluating their association with recurrence, disease-free survival and overall survival through statistical analysis. In the part corresponding to piRNAs, expression levels between LUAD and LUSC were compared to identify potential differences between subtypes, applying multivariate statistical models to determine their involvement in the stratification of recurrence risk. In addition, in cell models of NSCLC, the role of circRNA-10720 and piRNAs in the proliferation, migration, invasion and regulation of EMT was evaluated. MTS and clonogenesis assays were performed to measure proliferative capacity, as well as wound healing and transwell assays to assess cell migration and invasion. A three-dimensional model of 3D organoids was also used to validate their biological effects, allowing a more physiological approach to their function in tumor progression. Main results: Expression analysis revealed that circRNA-10720 and selected piRNAs showed significant differences between tumor and normal tissues in patients with resectable NSCLC. Functional assays in cell lines indicated that circRNA-10720 and hsa_piR_004530 promote cell proliferation, migration and invasion, and that circRNA-10720 also plays a regulatory role in the epithelial-mesenchymal transition. Conclusions: The results of this study indicate that circRNA-10720 and the piRNAs analyzed are associated with the postoperative prognosis of NSCLC, especially in LUSC, suggesting their potential as prognostic biomarkers and therapeutic targets for personalized strategies.
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HE, Yangyi. CircRNA and piRNAs as Biomarkers in Non-Small Cell Lung Cancer: Their Role in Tumor Progression and Patient Outcome. [consulta: 5 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/224587]