Exploratory transcriptomic analysis of low-grade oral epithelial dysplasia and oral squamous cell carcinoma in Chilean patients

Background: To explore and characterize gene expression patterns and RNA-seq–derived sequence variation in samples from Chilean patients with low-grade oral epithelial dysplasia (LG-OED) and oral squamous cell carcinoma (OSCC). Methods and Results: Transcriptome sequencing was performed on pooled samples of 5 LG-OED and compared with 5 OSCC and healthy oral mucosa tissue. Subsequently, a variation analysis of the transcriptome was conducted, along with functional classification of the most enriched signaling pathways. Dysregulated genes were found in both LG-OED and OSCC compared to the control groups. The most overexpressed genes were KRTAP5-4, LCE3B, DDX3Y, KDM5D, and MYH2, while the most repressed genes were TYRP1, HS3ST6, SNORA20, KRT76, TGM7, and SOX21 in LG-OED and OSCC, respectively. A large proportion of the identified variants were single nucleotide polymorphisms (SNPs). Based on frameshift effects, missense mutations were the most common. The most enriched signaling pathways in LG-OED were the Hippo, NOTCH, and TGF-beta pathways; in OSCC, the NRF2, TGF-beta, and PI3K pathways. Conclusions: This exploratory study provides an initial molecular characterization of LG-OED and OSCC in Chilean patients, identifying candidate transcriptomic alterations and RNA-seq–derived variants that may contribute to understanding early oral carcinogenesis in this underrepresented population.