Bioinformatics Analysis of the Prognostic and Biological Significance of ZDHHC-Protein Acyltransferases in Kidney Renal Clear Cell Carcinoma.
Bioinformatics Analysis of the Prognostic and Biological Significance of ZDHHC-Protein Acyltransferases in Kidney Renal Clear Cell Carcinoma.
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DOI：
10.3389/fonc.2020.565414
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发表时间：
2020
影响因子：
4.7
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Liu Z;Liu C;Xiao M;Han Y;Zhang S;Xu B
ZDHHC-蛋白酰基转移酶（ZDHHC）是一个由23个特征性Asp-His-His-Cys（DHHC）结构域组成的酶家族，其通过将16碳脂肪酸棕榈酸酯共价连接到底物蛋白中特定半胱氨酸残基的巯基来介导棕榈酰化。新出现的证据表明，ZDHHCs在各种疾病状态中的异常表达，包括癌症。肾透明细胞癌（KIRC）是第八种最常见的癌症类型，占恶性肾脏肿瘤的大多数。然而，目前还没有有效的治疗靶点或生物标志物用于KIRC的临床治疗和预后。在本研究中，我们首先使用TCGA和GEPIA数据库分析了23种ZDHHC在KIRC中的表达模式，发现ZDHHC 2，3，6，14，15，21和23的表达在KIRC患者组织中与正常组织相比显著下调，而ZDHHC 9，17，18，19和20的表达显著上调。ZDHHC 2、3、6、9、14、15、21在KIRC中的表达随病理分期的增加而降低。值得注意的是，具有ZDHHC 3、6、9、14、15、17、20、21、23的表达降低和ZDHHC 19的表达升高的KIRC患者与不良预后显著相关。进一步，我们发现ZDHHC 3、6、9、14、15、17、19、20、21、23的表达与免疫细胞浸润之间存在显著相关性。此外，高mRNA表达是最常见的基因改变类型，并且ZDHHC 6、17、20和21的表达之间具有高度相关性。功能预测提示，ZDHHC异常表达所导致的免疫或代谢紊乱或致癌信号通路的激活可能是KIRC患者肿瘤进展和预后不良的重要机制。我们的研究结果可能为识别肿瘤标志物或治疗KIRC的分子靶点提供新的见解。
ZDHHC-protein acyltransferases (ZDHHCs) are a family of 23 signature Asp-His-His-Cys (DHHC) domain-containing enzymes that mediate palmitoylation by covalent attachment of the 16-carbon fatty acid palmitate to thiol groups of specific cysteine residues in substrate proteins. Emerging evidence has shown abnormal expression of ZDHHCs in a variety of disease states, including cancer. Kidney renal clear cell carcinoma (KIRC) is the eighth most common type of cancer, which accounts for the majority of malignant kidney tumors. However, there are currently no effective therapeutic targets or biomarkers for clinical treatment and prognosis in KIRC. In this study, we first analyzed the expression pattern of the 23 ZDHHCs in KIRC using TCGA and GEPIA database, and found that the expression of ZDHHC2, 3, 6, 14, 15, 21, and 23 was significantly down-regulated whereas the expression of ZDHHC9, 17, 18, 19 and 20 was significantly up-regulated in KIRC patient tissues vs. normal tissues. And the expression of ZDHHC2, 3, 6, 9, 14, 15, and 21 in tumors decreased with the increase of the pathological stage of KIRC patients. Notably, KIRC patients with decreased expression of ZDHHC3, 6, 9, 14, 15, 17, 20, 21, 23 and increased expression of ZDHHC19 were significantly associated with poor prognosis. Further, we found that there was a significant correlation between ZDHHC3, 6, 9, 14, 15, 17, 19, 20, 21, 23 expressions and immune cell infiltration. Besides, high mRNA expression was the most common type of gene alteration and there was a high correlation among the expression of ZDHHC6, 17, 20 and 21. Finally, function prediction indicated that the immune or metabolic disorders or the activation of oncogenic signaling pathways caused by abnormal expression of these ZDHHCs may be important mechanisms of tumor progression and poor prognosis in patients with KIRC. Our results may provide novel insight for identifying tumor markers or molecular targets for the treatment of KIRC.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1038/nrurol.2010.47
发表时间：
2010-05
期刊：
Nature reviews. Urology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1136/bmj.g4797
发表时间：
2014-11-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Jonasch E;Gao J;Rathmell WK
通讯作者：
Rathmell WK
影响因子：
16
作者：
Runkle KB;Kharbanda A;Stypulkowski E;Cao XJ;Wang W;Garcia BA;Witze ES
通讯作者：
Witze ES
影响因子：
11.2
作者：
Sharma C;Wang HX;Li Q;Knoblich K;Reisenbichler ES;Richardson AL;Hemler ME
通讯作者：
Hemler ME