High tyrosine threonine kinase expression predicts a poor prognosis: a potential therapeutic target for endometrial carcinoma

Chun-Hong Cui; Qi Wu; Hong-Mei Zhou; Haiju He; Yan Wang; Zhendong Tang; Yi Zhang; Xue Wang; Jie Xiao; Hao Zhang

doi:10.21037/atm-22-5783

High tyrosine threonine kinase expression predicts a poor prognosis: a potential therapeutic target for endometrial carcinoma

Ann Transl Med. 2022 Dec;10(24):1352. doi: 10.21037/atm-22-5783.

Authors

Chun-Hong Cui^#¹, Qi Wu^#², Hong-Mei Zhou³, Haiju He⁴, Yan Wang⁵, Zhendong Tang⁶, Yi Zhang⁷, Xue Wang⁸, Jie Xiao⁹, Hao Zhang⁵

Affiliations

¹ Basic Medical College, Shanghai University of Medicine and Health Sciences, Shanghai, China.
² Department of Clinical Laboratory, Shanghai 10th People's Hospital of Tongji University, Shanghai, China.
³ Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
⁴ Department of Hematology, Soochow University Affiliated No. 1 People's Hospital, Suzhou, China.
⁵ Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ School of Data Science and Engineering, East China Normal University, Shanghai, China.
⁷ Department of Inorganic Materials, School of Minerals Processing and Bioengineering, Central South University, Changsha, China.
⁸ Department of Dermatology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁹ Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

^# Contributed equally.

Abstract

Background: As the most common female malignancy, the incidence and mortality of endometrial carcinoma (EC) continue to increase worldwide. The effects of traditional standard therapy are limited; thus, novel therapeutic strategies urgently need to be developed. We sought to provide prospective targeting insights into EC therapeutics by comprehensively examining and confirming the biological molecular characterization of EC genes.

Methods: The molecular characterization of EC genes was integrated and analyzed using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) databases. The differentially expressed genes (DEGs) were identified, and the abnormal expression of some core cell-cycle proteins in the EC specimens was determined by examining and integrating the TCGA and GTEx data. The enriched signaling pathways involved in tumor progression were also examined.

Results: Immunohistochemical staining data from the Human Protein Atlas database showed that the differential expression levels of the cyclin dependent kinase inhibitor 2A (CDKN2A) and tyrosine threonine kinase (TTK) molecules, and the high messenger ribonucleic acid (RNA) levels of CDKN2A and TTK were associated with a poor prognosis in EC patients. High TTK expression was also significantly correlated with the tumor progression associated signaling pathways, such as the cell-cycle, nucleolus, and RNA processing pathways. The inhibition of TTK expression by a TTK inhibitor (NTRC0066-0) significantly suppressed the proliferation of the EC cells and synergistically increased the sensitivity of the EN and AN3-CA EC cell lines.

Conclusions: The findings suggest that the TTK inhibitor could be used in EC therapy. This study highlighted the potential predictive role of TTK molecules and showed that TTK molecules might serve as prospective targets for EC therapy.

Keywords: Endometrial carcinoma (EC); TTK inhibitor; cell cycle; cyclin dependent kinase inhibitor 2A (CDKN2A); tyrosine threonine kinase (TTK).