Int J Med Sci 2020; 17(18):3112-3124. doi:10.7150/ijms.49652

Research Paper

Gene signatures and prognostic analyses of the Tob/BTG pituitary tumor-transforming gene (PTTG) family in clinical breast cancer patients

Chung-Che Wu1#, Titus Ime Ekanem2,3#, Nam Nhut Phan4, Do Thi Thuy Loan5, Sz-Ying Hou5, Kuen-Haur Lee2,5,6,7✉, Chih-Yang Wang2,5✉

1. Division of Neurosurgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
2. PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan.
3. Department of Hematology, University of Uyo, Uyo 520221, Nigeria.
4. NTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City 700000, Vietnam.
5. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
6. Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
7. TMU Research Center of Cancer Translational Medicine, Taipei 11031, Taiwan.
#These authors contributed equally to this work.

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Citation:
Wu CC, Ekanem TI, Phan NN, Loan DTT, Hou SY, Lee KH, Wang CY. Gene signatures and prognostic analyses of the Tob/BTG pituitary tumor-transforming gene (PTTG) family in clinical breast cancer patients. Int J Med Sci 2020; 17(18):3112-3124. doi:10.7150/ijms.49652. Available from https://www.medsci.org/v17p3112.htm

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Abstract

Breast cancer is the most common cancer type in females, and exploring the mechanisms of disease progression is playing a crucial role in the development of potential therapeutics. Pituitary tumor-transforming gene (PTTG) family members are well documented to be involved in cell-cycle regulation and mitosis, and contribute to cancer development by their involvement in cellular transformation in several tumor types. The critical roles of PTTG family members as crucial transcription factors in diverse types of cancers are recognized, but how they regulate breast cancer development still remains mostly unknown. Meanwhile, a holistic genetic analysis exploring whether PTTG family members regulate breast cancer progression via the cell cycle as well as the energy metabolism-related network is lacking. To comprehensively understand the messenger RNA expression profiles of PTTG proteins in breast cancer, we herein conducted a high-throughput screening approach by integrating information from various databases such as Oncomine, Kaplan-Meier Plotter, Metacore, ClueGo, and CluePedia. These useful databases and tools provide expression profiles and functional analyses. The present findings revealed that PTTG1 and PTTG3 are two important genes with high expressions in breast cancer relative to normal breast cells, implying their unique roles in breast cancer progression. Results of our coexpression analysis demonstrated that PTTG family genes were positively correlated with thiamine triphosphate (TTP), deoxycytidine triphosphate (dCTP) metabolic, glycolysis, gluconeogenesis, and cell-cycle related pathways. Meanwhile, through Cytoscape analyzed indicated that in addition to the metastasis markers AURKA, AURKB, and NDC80, many of the kinesin superfamily (KIF) members including KIFC1, KIF2C, KIF4A, KIF14, KIF20A, KIF23, were also correlated with PTTG family transcript expression. Finally, we revealed that high levels of PTTG1 and PTTG3 transcription predicted poor survival, which provided useful insights into prospective research of cancer associated with the PTTG family. Therefore, these members of the PTTG family would serve as distinct and essential prognostic biomarkers in breast cancer.

Keywords: PTTG1, PTTG2, PTTG3, Breast cancer, Bioinformatics