Tre2-Bub2-Cdc16 Family Proteins Based Nomogram Serve as a Promising Prognosis Predicting Model for Melanoma.
Tre2-Bub2-Cdc16 Family Proteins Based Nomogram Serve as a Promising Prognosis Predicting Model for Melanoma.
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基于 Tre2-Bub2-Cdc16 家族蛋白的列线图可作为黑色素瘤有前景的预后预测模型
DOI：
10.3389/fonc.2020.579625
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发表时间：
2020
影响因子：
4.7
通讯作者：
Chen XP
中科院分区：
文献类型：
--
作者：
Tang L;Peng C;Zhu SS;Zhou Z;Liu H;Cheng Q;Chen X;Chen XP
Tre2-Bub2-Cdc16（TBC）蛋白在真核生物中是保守的，并作为负反馈控制Rab GTP酶的GAP，而TBC蛋白在黑色素瘤中的功能尚不清楚。在这项研究中，我们观察了33个TBC基因的差异表达的TCGA数据集分类的临床特征。LASSO考克斯回归分析筛选出7个结核病相关基因。突变分析显示，在7个结核病相关的TBCs中，高评分和低评分病例之间的频率变化不同。LASSO考克斯回归和一致聚类分析的高危评分和聚类1与临床特征和不良预后相关。GSVA分析表明，血栓相关TBCs与代谢和蛋白转运信号通路有关。相关性分析表明，侵袭相关TBCs与RAB家族成员、侵袭相关基因和免疫细胞之间存在相关性。预后诺模图模型已被很好地建立，以预测黑色素瘤的生存。此外，在体外实验中，我们还证实了对七种TBC蛋白之一的TBC1D7的干扰可以抑制黑色素瘤细胞的增殖、迁移和侵袭。综上所述，我们通过多种生物信息学分析和实验验证，初步探讨了TBCs对黑色素瘤的影响，有助于阐明黑色素瘤的发病机制和抗肿瘤药物的开发。
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 cellsin 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.
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影响因子：
4.8
作者：
Kane, S;Sano, H;Lienhard, GE
通讯作者：
Lienhard, GE
影响因子：
9.8
作者：
Dorval, Guillaume;Kuzmuk, Valeryia;Antignac, Corinne
通讯作者：
Antignac, Corinne
影响因子：
29
作者：
Chen S;Wasserman DH;MacKintosh C;Sakamoto K
通讯作者：
Sakamoto K
影响因子：
13.8
作者：
Liu-Smith F;Ziogas A
通讯作者：
Ziogas A
影响因子：
50.3
作者：
Houghton, AN;Polsky, D
通讯作者：
Polsky, D