Molecular, histopathological, and functional characterization of the dysregulation of the splicing machinery in lung carcinoids

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Introduction: Alteration of alternative splicing is an emerging hallmark of cancer, which has been linked to aggressiveness features in diverse types of tumors, including neuroendocrine neoplasms.

Aim(s): The aim of the work was to explore splicing dysregulation in lung carcinoids (LC) by applying an integrated approach comprising biocomputational, histopathological and functional/mechanistic assays.

Materials and methods: Expression of 43 splicing-related genes was evaluated in a discovery cohort of 33 LC using a microfluidic custom-made array and validated in an external cohort of 51 samples (GSE105055). We explored their association with clinical parameters and employed immunohistochemistry to test specific molecular targets. A splicing-specific biocomputational analysis was carried out on RNA-seq data from an additional cohort of 20 patients. Finally, in vitro assays were performed using two LC cell lines, UMC-11 and NCI-H727.

Conference:

Presenting Author: García Vioque V

Authors: García-Vioque V, Blázquez-Encinas R, Caro-Cuenca T, Moreno-Montilla M, Alors-Pérez E,

Keywords: lung carcinoid, splicing dysregulation, splicing events, splicing machinery,