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.
Highlights
Melanoma is the most aggressive skin tumor that accounts for 90% of the deaths caused by skin cancer [1]
A total of 33 TBC family members were shown in the the Cancer Genome Atlas (TCGA) dataset. mRNA expression levels of some of the TBCs genes were closely related to some clinical traits of melanoma such as tumor type, tumor status, age, gender and stage
Different from the study by Qi et al, we investigated the association of mRNA expression of TBCs and the clinical traits in melanoma, and we observed that in spite of TBC1D7, six other prognostic-associated TBC genes TBC1D13, TBC1D16, TBC1D7, TBC1D8B, TBC1D15, TBC1D19, and TBC1D10C were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis In addition, mutations profile of these genes was analyzed
Summary
Melanoma is the most aggressive skin tumor that accounts for 90% of the deaths caused by skin cancer [1]. The incidence has been continuously rising over the past decades with about 232,100 new cases and 55,500 deaths annually. In 2012, the world standard incidence fluctuated from 0.2 in southeast Asia to 7.7 in America, 10.2 in EU and 13.8 in North America every 100,000 people years [2]. At the early stage of tumor progression, surgical resection is the primary approach to convincing a good prognosis. Once it progresses to stages of metastasis, it’s hard to cure owing to therapy resistance and recurrence in spite of the application of targeted therapy and immunotherapy [5, 6]. There is an urgent need to clarify the complexity of pathogenesis during the progression and treatment of melanoma
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