Identification and Clinical Validation of Genes Signatures with Grade and Survival in Head and Neck Carcinomas

Background: The mechanism of transition from low-grade to high-grade head and neck carcinomas (HNC) still remains unclear. This study aimed to explore the genes expression profiles that drive malignancy from low to high-grade HNC, as well as analyze their correlations with survival.Methods: Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly different genes (SDGs) between low and high-grade HNC were screened by GEO2R tool and R software. Bioinformatics functions of SDGs were investigated by the enrichment analyses. Univariate and multivariate cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating curve (ROC) was established to evaluate the ability to predict the prognosis. Then, the correlations between SDGs and clinical features were evaluated. The genes were experimentally validated by RT-PCR in clinical specimens.Results: 35 SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Enrichment analysis showed these SDGs were enriched in the DNA repair pathway and the regulation of I−kappaB kinase/NF−kappaB signaling pathway. Cox regression analyses showed that CXCL14, SLC44A1 and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients at a high-risk or low-risk for prognosis were established based on genes signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033, 0.010 respectively). Multivariate cox regression showed human papillomavirus (HPV) (P=0.033), lymph node status (P=0.032) and residual status (P＜0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858, 0.901 respectively). In addition, we found UBD, PPP2R2C and risk score were significantly associated with HPV status (all P＜0.05). The experiment results showed CXCL14 and SLC44A1 were significantly overexpressed in the HNC grade I/II tissues and the UBD was overexpressed in the HNC grade III/IV tissues.Conclusions: Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarker to predict the survival.