Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer

作者：Miao Yu, Yosuke Konno, Baojin Wang, Lin Zhu, Tianyue Zhai, Kei Ihira, Noriko Kobayashi, Hidemichi Watari, Xin Jin, Junming Yue, Peixin Dong, Mingyan Fang · 发表于：Journal of Translational Medicine · 年份：2023 · DOI：10.1186/s12967-023-03998-8 · 被引用次数：22 · 研究领域：Immunotherapy and Immune Responses、MicroRNA in disease regulation、Ferroptosis and cancer prognosis

Abstract Background Cancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase ( TTK ) in EC are yet to be fully understood. Methods Using bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells. Results We identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with E...