Background: Transcriptional dysregulation is one of the most important features of cancer genesis and progression. Applying gene expression dysregulation information to predict the development of cancers is useful for cancer diagnosis. However, previous studies mainly focused on the relationship between a single gene and cancer. Prognostic prediction using combined gene models remains limited.
Materials and methods: Gene expression profiles were downloaded from The Cancer Genome Atlas and the data sets were randomly divided into training data sets and test data sets. A six-gene signature associated with head and neck squamous cell carcinoma (HNSCC) and overall survival (OS) was identified according to a training cohort by using weighted gene correlation network analysis and least absolute shrinkage and selection operator Cox regression. The test data set and gene expression omnibus (GEO) data set were used to validate this signature.
Results: We identified six candidate genes, namely, FOXL2NB, PCOLCE2, SPINK6, ULBP2, KCNJ18, and RFPL1, and, using a six-gene model, predicted the risk of death of head and neck squamous cell carcinoma in The Cancer Genome Atlas. At a selected cutoff, patients were clustered into low- and high-risk groups. The OS curves of the two groups of patients had significant differences, and the time-dependent receiver operating characteristics of OS, disease-specific survival (DSS), and progression-free survival (PFS) were as high as 0.766, 0.731, and 0.623, respectively. Then, the test data set and the GEO data set were used to evaluate our model, and we found that the OS time in the high-risk group was significantly shorter than in the low-risk group in both data sets, and the receiver operating characteristics of test data set were 0.669, 0.675, and 0.614, respectively. Furthermore, univariate and multivariate Cox regression analyses showed that the risk score was independent of clinicopathological features.
Conclusion: The six-gene model could predict the OS of HNSCC patients and improve therapeutic decision-making.
Keywords: gene expression dysregulation, TCGA, six-gene model, OS