Abstract
Dysregulated metabolic pathways have been appreciated to be intimately associated with tumorigenesis and patient prognosis. Here, we sought to develop a novel prognostic signature based on metabolic pathways in patients with primary oral squamous cell carcinoma (OSCC). The original RNA-seq data of OSCC from The Cancer Genome Atlas (TCGA) project and Gene Expression Omnibus (GEO) database were transformed into a metabolic pathway enrichment score matrix by single-sample gene set enrichment analysis (ssGSEA). A novel prognostic signature based on metabolic pathways was constructed by LASSO and stepwise Cox regression analysis in the training cohort and validated in both testing and validation cohorts. The optimal cut-off value was obtained using the Youden index by receiver operating characteristic (ROC) curve. The overall survival curves were plotted by the Kaplan-Meier method. A time-dependent ROC curve analysis with 1, 3, 5 years as the defining point was performed to evaluate the predictive value of this prognostic signature. A 5-metabolic pathways prognostic signature (5MPS) for OSCC was constructed which stratified patients into subgroups with favorable or inferior survival. It served as an independent prognostic factor for patient survival and had a satisfactory predictive performance for OSCC. Our results developed a novel prognostic signature based on dysregulated metabolic pathways in OSCC and provided support for aberrant metabolism underlying OSCC tumorigenesis.
Highlights
Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck region which is closely associated with smoking and alcohol abuse [1]
The original head and neck squamous cell carcinoma (HNSCC) RNAseq data were downloaded from The Cancer Genome Atlas (TCGA) database and all oral squamous cell carcinoma (OSCC) relevant datasets were further retrieved from TCGA-HNSC dataset
We identified 75 dysregulated metabolic pathways which significantly differed between OSCC and normal samples with FDR
Summary
Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the head and neck region which is closely associated with smoking and alcohol abuse [1]. It is frequently treated with a combination of surgery, radiotherapy and chemotherapy in the clinic. Metabolic Prognostic Signature for OSCC and metabolic events underlying oral tumorigenesis as well as the lack of effective prognostic predictors and therapeutic targets [3] These traditional prognostic indicators such as tumor size, margin status and tumor stage remain far from optimal and usually fail to meet clinical needs due to substantial survival variations in patients within the same catalogs [2, 4]. It is necessary and urgently required to identify new, effective, sensitive biomarkers for early detection, diagnosis and prognosis of OSCC
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