Transcriptome-wide profiling of cystic and solid vestibular schwannomas reveals candidate long non-coding RNA signatures

Vestibular schwannoma (VS) is a benign tumor growing from Schwann cells of the vestibulocochlear nerve (cranial nerve VIII), accounting for 6-8% of brain tumors. Cystic vestibular schwannoma (cVS) represents 10% of VS cases and is characterized by unpredictable growth and worse surgical outcomes compared to solid VS (sVS). The molecular mechanisms underlying this aggressive phenotype remain poorly understood. In this context, long non-coding RNAs (lncRNAs) are gaining increased interest as biomarkers for early diagnosis and improved clinical management. lncRNAs are RNA molecules that are longer than 200 nucleotides. They are known to regulate gene transcription and participate in chromatin remodeling through various mechanisms. However, their role in cVS is largely unexplored. In this study, we identified cVS-associated lncRNAs using patient-derived samples. Whole transcriptome analysis via RNA sequencing revealed 65 differentially expressed lncRNAs and 308 protein-coding genes (PCGs) between cVS and sVS. From these, we selected the top eight lncRNAs (TENM3-AS1, ADIRF-AS1, PCA3, RP11-108K14.12, RP11-728F11.4, AC132217.4, RP11-43F13.3, and EGFLAM-AS1), each showing significant correlation with more than 20 differentially expressed PCGs. The upregulation of PCA3 and ADIRF-AS1, and the downregulation of EGFLAM-AS1 in cVS, were further validated using qRT-PCR. Here, by transcriptome-wide approach, we demonstrate that lncRNAs are prevalent in cVS disease and are likely to play critical roles in regulating important signaling pathways involved in disease pathogenesis. We believe, that detailed future investigations on this set of identified lncRNAs can provide useful insights into the biology and, ultimately, contribute to biomarker development for this neoplasm.