YTHDF3as a prognostic predictive biomarker of thyroid cancer and its correlation with immune infiltration
Yihan Zhang,
Ying Chen,
Ruihua Chen,
Hong Zhou,
Yi Lin,
Bingxin Li,
Huaidong Song,
Guoqiang Zhou,
Mei Dong,
Huanbai Xu
Affiliations
Yihan Zhang
Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Ying Chen
Department of Endocrinology and Metabolism, Changhai Hospital of Shanghai
Ruihua Chen
Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Hong Zhou
Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Yi Lin
Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Bingxin Li
Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Huaidong Song
Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Guoqiang Zhou
Department of General Surgery, The Affiliated Changshu Hospital of Xuzhou Medical University
Mei Dong
Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Huanbai Xu
Department of Endocrinology and Metabolism, Center for Microbiota and Immunological Diseases, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University
Abstract Purpose Thyroid cancer (TC) is one of the most common endocrine malignancies, and its morbidity continues to rise. N6-methyladenosine (m6A) RNA methylation, an epigenetic modification, is an important regulator of gene expression in TC. Therefore, it’s worth finding the characteristics and predictive value of the m6A RNA methylation regulators in thyroid cancer (TC). Method RNA-seq data of TC was downloaded from the Cancer Genome Atlas (TCGA) database to screen out the differential expressed regulators. The absolute contraction selection operator (Lasso) Cox regression was used to construct the risk model of m6A methylation regulators. The predictive value of the risk scoring model was evaluated by Kaplan Meier (K-M) analysis and receiver operating characteristic (ROC) curves. The underlying mechanism of m6A methylation regulators in TC was predicted by gene set enrichment analysis (GSEA). Further validation was performed by using immunohistochemistry (IHC) and q-PCR. The correlation between risk-related gene and immune infiltration was evaluated by Tumour Immune Estimation Resource (TIMER). Results IGF2BP2, YTHDF1 and YTHDF3 were screened out as strong independent prognostic factors of TC. Then a risk score model was established to further screen the predictors. Finally, according to the results of overall survival (OS) and clinical characteristics of TC, YTHDF3 was screened out as a potential predictor. Meanwhile, IHC and qPCR confirmed that YTHDF3 was expressed differential in TC. The expression of YTHDF3 was positively associated with the infiltration level of CD4+ T cells and macrophages. It was strongly correlated with a variety of immune markers in TC. Conclusion We confirmed that YTHDF3 can be used as a potential prognostic biomarker of TC. It not only plays a decisive role in the initiation and development of TC, but also provides a new perspective for understanding the modification of m6A RNA in TC.
