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Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Genetic alteration involving N6-methyladenosine (m6A) regulatory genes is a frequent characteristic of multiple tumors. Nevertheless, little is known regarding their genetic alteration signatures and prognostic values in head and neck squamous cell carcinoma (HNSCC). In this study, RNA sequence profiles and copy number variation (CNV) data of 506 HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Correlation analysis involving alteration of m6A regulatory genes, clinicopathological characteristics, and patient survival was performed using R language. The results suggest that alteration of m6A regulatory genes was correlated with clinical staging. Patients with high expression of ALKBH5, FTO, METTL14, WTAP, YTHDC1, YTHDF1, and YTHDF2 had poor overall survival (OS) than those with low expression. Univariate and multivariate Cox regression analyses showed that ALKBH5 and YTHDC2 were independent risk factors for OS. However, patients with high YTHDC2 expression had better OS. Moreover, according to machine learning results, YTHDC2 was found to be the most important gene among the 10 m6A regulators. Additionally, high expression of YTHDC2 was correlated with activation of apoptosis and ubiquitin-mediated proteolysis. Here, we identified alterations to m6A regulatory genes in HNSCC for the first time and found that seven m6A regulators were associated with poor prognosis, especially ALKBH5, whereas YTHDC2 was associated with better prognosis. These m6A-related regulators could act as novel prognostic biomarkers for HNSCC. Our findings provide clues for understanding RNA epigenetic modifications in HNSCC.

SUBMITTER: Zhou X

PROVIDER: S-EPMC7273190 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma.

Zhou Xuanchen X Han Jie J Zhen Xiaoyue X Liu Yiqing Y Cui Zhaoyang Z Yue Zhiyong Z Ding Ling L Xu Shuai S

Frontiers in oncology 20200529

Genetic alteration involving N6-methyladenosine (m6A) regulatory genes is a frequent characteristic of multiple tumors. Nevertheless, little is known regarding their genetic alteration signatures and prognostic values in head and neck squamous cell carcinoma (HNSCC). In this study, RNA sequence profiles and copy number variation (CNV) data of 506 HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Correlation analysis involving alteration of m6A regulatory genes, clinico ...[more]

PMID: 32547941

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Project description:OBJECTIVES:Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer. MATERIALS AND METHODS:Native T1-weighted images of four independent, retrospective (2005-2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC). RESULTS:In oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001). CONCLUSIONS:MRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters. KEY POINTS:• MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer. • MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models. • Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models.

Dataset Information

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma.

Publications

Analysis of Genetic Alteration Signatures and Prognostic Values of m6A Regulatory Genes in Head and Neck Squamous Cell Carcinoma.

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