Background. There are few informations about the molecular events involved in the pathogenesis of sinonasal intestinal-type adenocarcinomas (ITACs). Moreover, although some of the classic prognostic factors (advanced pT classification, high-grade, and positive surgical margins) continue to be very useful in predicting the clinical behavior of ITACs, it is still unclear why some patients have a better prognosis than others with the same type of lesion in terms of histological characteristics and clinical stage. The purpose of this study was to identify in a well-characterized and homogeneous cohort of patients with ITAC, through a miRNoma analysis, a specific microRNAs (miRNAs) profile, and to assess their clinical and prognostic significance. Methods. Patients with ITAC who underwent endoscopic surgery  RT at two centers were retrospectively reviewed. miRNoma analysis has been performed using Next Generation Sequencing (NGS) technology in tumor and adjacent healthy tissue; among these, based on the expression and the distribution in characteristic clusters of the pathology, 4-miRNAs (miR-34c, miR-192, miR-205, miR-449a) were selected, which were subsequently validated on the population of ITAC patients. In order to assess the clinical value, the expression of the 4-miRNAs has been associated with the outcome of the patients. In addition, overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier curve and miRNA groups (below and above the median) were compared using the log-rank test. Cox multivariate regression analysis was used to evaluate independent survival prediction factors. A value of p <0.05 was considered statistically significant. All statistical analyzes were performed using SPSS for Windows version 19.0 (SPSS Inc, Chicago, IL). Results. Fortythree patients were included. The results of our study showed that both miR-205 and miR- 449a are independent biomarkers for recurrence in patients with sinonasal ITAC. In particular, the over-expression of the two miRNAs was associated with a higher risk of recurrence and therefore with a worse prognosis. The multivariate analysis confirms their independent predictive value. Conclusion. Our results highlights that an over-expression of miR-205 and miR-449a in sinonasal ITAC is associated with an increased risk of recurrence (reduced DFS) and reduced OS, suggesting that mutation of these miRNAs in combination with additional genetic events, could play a significant role in the pathogenesis of ITAC.

Mirnoma analysis in sinonasal intestinal-type adenocarcinoma: identification of micrornas profile and its clincal and prognostic significance

BAJRAKTARI, ARISA
2020-10-29

Abstract

Background. There are few informations about the molecular events involved in the pathogenesis of sinonasal intestinal-type adenocarcinomas (ITACs). Moreover, although some of the classic prognostic factors (advanced pT classification, high-grade, and positive surgical margins) continue to be very useful in predicting the clinical behavior of ITACs, it is still unclear why some patients have a better prognosis than others with the same type of lesion in terms of histological characteristics and clinical stage. The purpose of this study was to identify in a well-characterized and homogeneous cohort of patients with ITAC, through a miRNoma analysis, a specific microRNAs (miRNAs) profile, and to assess their clinical and prognostic significance. Methods. Patients with ITAC who underwent endoscopic surgery  RT at two centers were retrospectively reviewed. miRNoma analysis has been performed using Next Generation Sequencing (NGS) technology in tumor and adjacent healthy tissue; among these, based on the expression and the distribution in characteristic clusters of the pathology, 4-miRNAs (miR-34c, miR-192, miR-205, miR-449a) were selected, which were subsequently validated on the population of ITAC patients. In order to assess the clinical value, the expression of the 4-miRNAs has been associated with the outcome of the patients. In addition, overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier curve and miRNA groups (below and above the median) were compared using the log-rank test. Cox multivariate regression analysis was used to evaluate independent survival prediction factors. A value of p <0.05 was considered statistically significant. All statistical analyzes were performed using SPSS for Windows version 19.0 (SPSS Inc, Chicago, IL). Results. Fortythree patients were included. The results of our study showed that both miR-205 and miR- 449a are independent biomarkers for recurrence in patients with sinonasal ITAC. In particular, the over-expression of the two miRNAs was associated with a higher risk of recurrence and therefore with a worse prognosis. The multivariate analysis confirms their independent predictive value. Conclusion. Our results highlights that an over-expression of miR-205 and miR-449a in sinonasal ITAC is associated with an increased risk of recurrence (reduced DFS) and reduced OS, suggesting that mutation of these miRNAs in combination with additional genetic events, could play a significant role in the pathogenesis of ITAC.
Sinonasal cancers, intestinal-type adenocarcinoma, biomarkers, miRNA
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11566/283977
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