Comprehensive RNA-seq analysis of alternative splicing events that distinguishes between metastatic oral cancer of gingiva and tongue

Differential splicing in oral cancer subtypes

Abstract

Oral cancer (OC) is a multifactorial disease caused due to various genomic changes. Alternative splicing (AS) is a regulatory genetic process through which messenger RNA forms diverse protein variants. This study aims to study the variation in the AS events at tongue and gingiva locations of OC.

Materials and Methods: Forty-five paired end OC RNA-seq data were downloaded from Sequence Read Archive (SRA) data repository. Twenty four paired end OC (tongue 13, gingival 11) RNA sequences passed the stringent inclusion/ exclusion criteria which were analyzed following Tuxedo pipeline. The ClueGO (v2.5.8) tool in Cytoscape app manager (v3.7.1) was used for gene set enrichment analysis keeping false discovery rate (FDR <=0.05).

Results: Eighty-three genes were identified to be significantly alternatively spliced when comparison was made between RNA sequences from normal tissues and tumor tissues from the gingiva region (p<0.05). Similarly, 39 genes were found to be significantly alternatively spliced when comparison was made between normal tissues and tumor tissues from tongue region of OC. Of these, only 4 genes i.e. AHR, AL356488.2, KREMEN1, SH3TC1 were similar in gingiva and tongue whereas others were unique to their location.

Conclusion: Genome-wide AS events vary considerably in gingival and tongue locations of OC. Hence, these events need to be thoroughly investigated for defining the treatment strategy. Further functional studies are needed to decipher the role of AS in OC.