Integrated analysis of lncRNA-associated ceRNA network in p16-positive and p16-negative head and neck squamous cell carcinoma.

Abstract

Determination of human papillomavirus (HPV) status has become clinically relevant for head and neck squamous cell carcinoma (HNSCC) patients. p16 immunohistochemistry is one of the recommended methods for classifying HPV status. However, long noncoding RNAs (lncRNAs) and related competing endogenous RNA (ceRNA) networks linked to different p16-status HNSCC are still absent.In the present study, The Cancer Genome Atlas database provided RNA profiles as well as clinical information from 26 p16-positive HNSCC samples, 71 p16-negative HNSCC samples, and 44 adjacent normal control samples. Differentially expressed RNAs (DERNAs) between HNSCC samples and normal samples were identified by limma package in R. Functional enrichment analysis of differentially expressed mRNAs was performed using Clusterprofiler package in R. Survival analysis of DERNAs was carried out by survival package in R. The ceRNA network was constructed using GDCRNATools package in R.A total of 102 lncRNAs, 196 microRNAs (miRNAs), and 2282 mRNAs were identified as p16-positive-specific DERNAs. There were 90 lncRNAs, 153 miRNAs, and 2038 mRNAs were identified as p16-negative-specific DERNAs. Functional enrichment analysis revealed that the differentially expressed mRNAs in the p16-positive and the p16-negative group were mainly enriched in the “DNA replication” and “extracellular matrix -receptor interaction” pathway, respectively. Among the top 25 DERNAs, there were 1 key lncRNA, 1 key miRNA, and 1 key messenger RNA in the p16-positive group and 2 key lncRNAs, 1 key miRNA, and 2 key mRNAs in the p16-negative group were significantly related to the overall survival. Then the ceRNA network in the p16-positive and p16-negative group was constructed. There were 5 lncRNAs, 16 miRNAs, and 66 mRNAs included in the p16-positive group ceRNA network and 1 lncRNA, 4 miRNAs, and 28 mRNAs included in the p16-negative group ceRNA network. Among the RNAs in the ceRNA network, 5 mRNAs were significantly related to the overall survival.Taken together, we revealed the differential RNA expression profiling and the differential ceRNA network in the p16-positive and p16-negative group of HNSCC. Our findings provided a novel insight into this HPV-related cancer and potential biomarkers and therapeutic targets for HNSCC based on p16 status.