Abstract
Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in “atypical 1 (IR)” HNSCC clusters, negatively influencing patients’ overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the “atypical 1 (IR)” subtype of HNSCC which influences both viral infection and patients’ survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients’ immune response, while on the other it can be favorable in virus replication.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide [1]
This study focuses on long non-coding RNA (lncRNA) associated with human papillomavirus (HPV) infection: CDKN2B-AS1 (ANRIL), TTTY14 (NCRNA00137), TTTY15 (NCRNA00138), PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) (NCRNA00074), XIST (NCRNA00001), MEG3 (NCRNA00023), H19 (NCRNA00008), MALAT1 (NCRNA00047), and CYTOR (NCRNA00152) [10]
81 HPV(−) and 40 HPV(+) head and neck squamous cell carcinoma (HNSCC) samples from The Cancer Genome Atlas (TCGA) with clinical data were included in the analysis
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide [1]. The best known risk factors for HNSCC are tobacco and alcohol exposure or dependence. Over the past decade, there has been an increase in oropharyngeal squamous cell carcinomas (OPCs) associated with the high-risk oncogenic human papillomavirus (HPV) [3]. Patients with HPV-positive (HPV+) OPC are usually middle-aged, non-smoking white men with a history of multiple sexual partners [4]. The prognosis for HPV(+) patients is significantly better than for those with tobacco-related HPV(−) carcinomas in cases of similar treatment [5]. Human papillomavirus has been identified as an independent risk factor for the development of HNSCC [6]
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