RESUMEN
BACKGROUND: Altered microRNA profiles have been observed not only in tumour tissues but also in biofluids, where they circulate in a stable form thus representing interesting biomarker candidates. This study aimed to identify a microRNA signature as a non-invasive biomarker and to investigate its impact on glioma biology. METHODS: MicroRNAs were selected using a global expression profile in preoperative serum samples from 37 glioma patients. Comparison between serum samples from age and gender-matched controls was performed by using the droplet digital PCR. The ROC curve and Kaplan-Meier survival analyses were used to evaluate the diagnostic/prognostic values. The functional role of the identified signature was assessed by gain/loss of function strategies in glioma cells. RESULTS: A three-microRNA signature (miR-1-3p/-26a-1-3p/-487b-3p) was differentially expressed in the serum of patients according to the isocitrate dehydrogenase (IDH) genes mutation status and correlated with both patient Overall and Progression Free Survival. The identified signature was also downregulated in the serum of patients compared to controls. Consistent with these results, the signature expression and release in the conditioned medium of glioma cells was lower in IDH-wild type cells compared to the mutated counterpart. Furthermore, in silico analysis of glioma datasets showed a consistent deregulation of the signature according to the IDH mutation status in glioma tumour tissues. Ectopic expression of the signature negatively affects several glioma functions. Notably, it impacts the glioma invasive phenotype by directly targeting the invadopodia-related proteins TKS4, TKS5 and EFHD2. CONCLUSIONS: We identified a three microRNA signature as a promising complementary or even an independent non-invasive diagnostic/prognostic biomarker. The signature displays oncosuppressive functions in glioma cells and impacts on proteins crucial for migration and invasion, providing potential targets for therapeutic intervention.
Asunto(s)
Neoplasias Encefálicas , MicroARN Circulante , Glioma , MicroARNs , Humanos , Neoplasias Encefálicas/patología , Biomarcadores de Tumor/genética , Glioma/patología , MicroARNs/genética , Pronóstico , Isocitrato Deshidrogenasa/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas de Unión al CalcioRESUMEN
The authors report the case of a patient affected by recurrent neuromas of the interdigital nerves of the left foot that appeared after surgery for Morton's disease. Implantation of spinal cord stimulation (SCS) system was performed after three unsuccessful surgical revisions, which demonstrated the presence of multiple neuromas growing at endings of the stumps of the nerves and fasciculi. The patient developed chronic neuropathic pain localized within the third metatarsal region of the left foot. Conservative treatments failed and autonomous gait became impossible. SCS immediately abolished pain and the patient was able to perform her normal daily activities within 1 month. At our knowledge, this is the first report in literature of SCS successfully employed for recurrent and refractory pain due to Morton's neuroma.