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

Deming Ou,Ying Wu

doi:10.1186/s12885-021-09058-y

Abstract

BackgroundIt 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.MethodsIn 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.ResultsWe 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.ConclusionsCollectively, 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.

Highlights

Head and neck cancer is the sixth most common malignant tumor in the world [1], and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer [2]
GSE138206 contained a total of 7133 differentially expressed genes (DEGs) between 10 normal samples and 5 cancerous samples; top 500 up- or down-regulated DEGs could form 114 reverse gene pairs with stable relative expression orderings (REOs)
In the present study, by analyzing DEGs in oral squamous cell carcinoma based on online datasets using the RankComp algorithm, we identified 6 reverse gene pairs with stable REOs

Summary

Introduction

Head and neck cancer is the sixth most common malignant tumor in the world [1], and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer [2]. Biomarkers could guide the selection of appropriate therapy by predicting disease activity and progression, by predicting which individuals will respond to a particular therapy, and by providing pharmacodynamic information to facilitate assessment of response to therapy [9, 10] It is a basic task in high-throughput gene expression profiling studies to identify differentially expressed genes (DEGs) between two phenotypes. Direct combining of multiple datasets could be hindered by various random factors including measurement batch effects [13] These problems pose key obstacles for the analysis of transcriptional data in The Cancer Genome Atlas (TCGA) where there are many small-scale batches of data. RankComp, an algorithm, could analyze the highly stable withinsample 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

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