The prognostic and clinical significance of IFI44L aberrant downregulation in patients with oral squamous cell carcinoma

Background: It is a basic task in high-throughput gene expression profiling studies to identify differentially expressed genes (DEGs) between two phenotypes. RankComp, an algorithm, could analyze the highly stable within-sample relative expression orderings (REOs) of gene pairs in a particular type of human normal tissue that are widely reversed in the cancer condition, thereby detecting DEGs for individual disease samples measured by a particular platform.

Methods: In the present study, Gene Expression Omnibus (GEO) Series (GSE) GSE75540, GSE138206 were downloaded from GEO, by analyzing DEGs in oral squamous cell carcinoma based on online datasets using the RankComp algorithm, using the Kaplan-Meier survival analysis and Cox regression analysis to survival analysis, Gene Set Enrichment Analysis (GSEA) to explore the potential molecular mechanisms underlying.

Results: We identified 6 reverse gene pairs with stable REOs. All the 12 genes in these 6 reverse gene pairs have been reported to be associated with cancers. Notably, lower Interferon Induced Protein 44 Like (IFI44L) expression was associated with poorer overall survival (OS) and Disease-free survival (DFS) in oral squamous cell carcinoma patients, and IFI44L expression showed satisfactory predictive efficiency by receiver operating characteristic (ROC) curve. Moreover, low IFI44L expression was identified as risk factors for oral squamous cell carcinoma patients' OS. IFI44L downregulation would lead to the activation of the FRS-mediated FGFR1, FGFR3, and downstream signaling pathways, and might play a role in the PI3K-FGFR cascades.

Conclusions: Collectively, we identified 6 reverse gene pairs with stable REOs in oral squamous cell carcinoma, which might serve as gene signatures playing a role in the diagnosis in oral squamous cell carcinoma. Moreover, high expression of IFI44L, one of the DEGs in the 6 reverse gene pairs, might be associated with favorable prognosis in oral squamous cell carcinoma patients and serve as a tumor suppressor by acting on the FRS-mediated FGFR signaling.