Abstract
High-throughput gene expression profiling has recently emerged as a promising technique that provides insight into cancer subtype classification and improved prediction of prognoses. Immune/inflammatory-related mRNAs may potentially enrich genes to allow researchers to better illustrate cancer microenvironments. Oral cavity squamous cell carcinoma (OC-SCC) exhibits high morbidity and poor prognosis compared to that of other types of head and neck squamous cell carcinoma (HNSCC), and these differences may be partially due to differences within the tumor microenvironments. Based on this, we designed an immune-related signature to improve the prognostic prediction of OC-SCC. A cohort of 314 OC-SCC samples possessing whole genome expression data that were sourced from The Cancer Genome Atlas (TCGA) database was included for discovery. The GSE41613 database was used for validation. A risk score was established using immune/inflammatory signatures acquired from the training dataset. Principal components analysis, GO analysis, and gene set enrichment analysis were used to explore the bioinformatic implications. When grouped by the dichotomized risk score based on the signature, this classifier could successfully discriminate patients with distinct prognoses within the training and validation cohorts (P < 0.05 in both cohorts) and within different clinicopathological subgroups. Similar somatic mutation patterns were observed between high and low risk score groups, and different copy number variation patterns were also identified. Further bioinformatic analyses suggested that the lower risk score group was significantly correlated with immune/inflammatory-related biological processes, while the higher risk score group was highly associated with cell cycle-related processes. The analysis indicated that the risk score was a robust predictor of patient survival, and its functional annotation was well established. Therefore, this bioinformatic-based immune-related signature suggested that the microenvironment of OC-SCC could distinguish among patients with different underlying biological processes and clinical outcomes, and the use of this signature may shed light on future OC-SCC classification and therapeutic design.
Highlights
Oral cavity squamous cell carcinoma (OC-SCC) is the most common malignancy of the head and neck region. ere has been a recent dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP-SCC) [1]
Different Immune/Inflammatory Phenotypes of OC-SCC Tumor. e gene expression and clinical data for 314 patients were obtained from the TCGA database (Table S1)
Risk factors such as tobacco use, alcohol consumption, and HPV infection have been proposed as initiating risk factors for OC-SCC [29,30,31]; there is little consensus on how immune/inflammatory responses could affect Overall survival time (OS)-SCC subtypes. e development of meaningful signatures to determine the immune status of patients provides an attractive therapeutic approach to this disease, as these signatures promise to be powerful prognostic biomarkers, but if properly applied, they stratify patients to increase the likelihood of positive outcomes in response to immunotherapy
Summary
Oral cavity squamous cell carcinoma (OC-SCC) is the most common malignancy of the head and neck region (excluding nonmelanoma skin cancer). ere has been a recent dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP-SCC) [1]. Oral cavity squamous cell carcinoma (OC-SCC) is the most common malignancy of the head and neck region (excluding nonmelanoma skin cancer). Ere are differences in the associated mortality, etiology, risk factors, and even the biomarkers of squamous cell carcinomas located within these two major sites. Many risk factors can contribute to OC-SCC. Tobacco smokers exhibit a 3.43 fold relative risk for OC-SCC compared to that of nonsmokers [2], and they possess a fully. Alcohol has been established as an independent risk factor, and studies of nonsmokers have demonstrated a strong correlation and dose-response relationship between alcohol consumption and OC-SCC [4]. HPV, as a major etiological factor, contributes disproportionally to the formation and prognosis of squamous cell carcinoma formation at different sites within the head and neck region [6]. A far more favorable outcome exists for HPV positive compared to that for HPVnegative OP-SCC [9]
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