Abstract
Increasing evidence suggests that N6-methyladenosine(m6A) has a vital role in cancer progression. Therefore, we aimed to explore the prognostic relevance of m6A-related genes in oral squamous cell carcinoma (OSCC). First, Expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and m6A-related genes were extracted afterwards. Then, cluster analysis and principal component analysis (PCA) were used to analyze m6A-related genes. And differentially-expressed analysis was performed in R software. Furthermore, a risk model was constructed, and crucial m6A genes were selected to explore its biological effects in OSCC cells. Total of 13 m6A-related genes were extracted and 8 differentially-expressed genes were identified. Subsequently, m6A-based clustering showed 2 subtypes with different clinical outcome. In addition, a risk model was successfully established. Of 13 m6A-related genes, only heterogeneous nuclear ribonucleoprotein C (HNRNPC) might be an independent biomarker and mean unfavorable overall survival in OSCC by univariate and multivariate cox regression analysis. Functional studies revealed that overexpression of HNRNPC promoted carcinogenesis of OSCC via epithelial- mesenchymal transition (EMT). In total, a risk model of m6A-related genes in OSCC was established. Subsequently, HNRNPC was proved to promote OSCC carcinogenesis and be an independent biomarker prognostic biomarker of OSCC, suggesting that it might be a new biomarker and therapeutic target of OSCC.
Highlights
As the most common oral cancer, oral squamous cell carcinoma (OSCC) is a serious global problem because of its most severe impact on life quality of patients [1]
RNA expression profiles and their corresponding clinical data of 317 OSCC samples and 32 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database, and the raw data were normalized in a log2(x + 1) manner
Expression profiles of 13 m6A-related genes including METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, heterogeneous nuclear ribonucleoprotein C (HNRNPC), FTO, ALKBH5 were extracted from the transcriptome data and 8 differentially expressed m6A-related genes were identified (Figure 1A, 1B)
Summary
As the most common oral cancer, oral squamous cell carcinoma (OSCC) is a serious global problem because of its most severe impact on life quality of patients [1]. Clinical data indicate that smoking, drinking and betel nut consumption are the main causes of the high incidence of OSCC. Leemans et al demonstrated that human papillomavirus (HPV) is considered as one of the potential risk factors of OSCC [2]. In spite of advancement in diagnosis and therapeutic methods, the prognosis of OSCC has not improved obviously over the past few years. High recurrence rate and lymph node metastasis risk lead to an unsatisfactory 5-year overall survival rate, which ranges from 45 to 50% [3]. It is imperative to further understand the potential mechanism of the initiation and progression in OSCC
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