Tre2-Bub2-Cdc16 Family Proteins Based Nomogram Serve as a Promising Prognosis Predicting Model for Melanoma

Ling Tang; Cong Peng; Su-Si Zhu; Zhe Zhou; Han Liu; Quan Cheng; Xiang Chen; Xiao-Ping Chen

doi:10.3389/fonc.2020.579625

Tre2-Bub2-Cdc16 Family Proteins Based Nomogram Serve as a Promising Prognosis Predicting Model for Melanoma

Front Oncol. 2020 Oct 28:10:579625. doi: 10.3389/fonc.2020.579625. eCollection 2020.

Authors

Ling Tang^{1

2

3}, Cong Peng^{3

4

5}, Su-Si Zhu^{1

2

3}, Zhe Zhou^{3

4

5}, Han Liu^{1

2}, Quan Cheng^{1

2

6}, Xiang Chen^{3

4

5}, Xiao-Ping Chen^{1

2}

Affiliations

¹ Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
² Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
³ Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
⁵ Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Tre2-Bub2-Cdc16 (TBC) proteins are conserved in eukaryotic organisms and function as negative feedback dominating the GAPs for Rab GTPases, while the function of TBC proteins in melanoma remains unclear. In this study, we observed the differential expression of 33 TBC genes in TCGA datasets classified by clinical features. Seven prognostic-associated TBC genes were identified by LASSO Cox regression analysis. Mutation analysis revealed distinctive frequency alteration in the seven prognostic-associated TBCs between cases with high and low scores. High-risk score and cluster 1 based on LASSO Cox regression and consensus clustering analysis were relevant to clinical features and unfavorable prognosis. GSVA analysis showed that prognostic-associated TBCs were related to metabolism and protein transport signaling pathway. Correlation analysis indicated the relationship between the prognostic-associated TBCs with RAB family members, invasion-related genes and immune cells. The prognostic nomogram model was well established to predict survival in melanoma. What's more, interference of one of the seven TBC proteins TBC1D7 was confirmed to inhibit the proliferation, migration and invasion of melanoma cells in vitro. In summary, we preliminarily investigated the impact of TBCs on melanoma through multiple bioinformatics analysis and experimental validation, which is helpful for clarifying the mechanism of melanoma and the development of anti-tumor drugs.

Keywords: Tre2-Bub2-Cdc16; melanoma; model; nomogram; prognostic.