DNA methylation of Hugl-2 is a prognostic biomarker in kidney renal clear cell carcinoma.
DNA methylation of Hugl-2 is a prognostic biomarker in kidney renal clear cell carcinoma.
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Hugl-2 DNA 甲基化是肾透明细胞癌的预后生物标志物
DOI：
10.1111/1440-1681.13390
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发表时间：
2021-01
影响因子：
2.9
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Miao Y;Cao F;Li P;Liu P
据报道，Hugl-2的缺失在体外和体内肿瘤的形成和发展中起到了重要作用。然而，肾透明细胞癌(KIRC)过程中Hugl-2水平是否降低及其机制尚不清楚。本研究旨在探讨Hugl-2基因甲基化是否降低其表达，从而导致KIRC的进展和预后不良。从癌症基因组图谱(TCGA)中提取Hugl-2甲基化、mRNA表达和KIRC临床病理数据，并使用UALCAN、MethHC、Wanderer和LinkedOmics网络工具分析这些因素之间的关系。我们发现KIRC组织中Hugl-2的mRNA和蛋白水平降低。此外，Hugl-2基因表达水平与肿瘤分级和总生存期有关，且KIRC中Hugl-2甲基化水平升高。根据甲基化特异性聚合酶链式反应的结果，KIRC细胞的Hugl-2 DNA甲基化水平高于HKC细胞。此外，Hugl-2DNA甲基化与Hugl-2mRNA的表达呈负相关，并与KIRC的病理类型和T分期有关。Hugl-2DNA甲基化水平高的KIRC患者总生存期也较短。此外，Hugl-2基因探针cg08827674的甲基化与病理分期、T分期、肿瘤组织学分级、无侧化的血钙水平、M分期、N分期和种族有关。此外，DNA甲基化抑制剂地西他滨处理导致KIRC细胞株Hugl-2的mRNA和蛋白水平上调。这些结果表明，Hugl-2DNA甲基化可能是KIRC的预后标志和治疗靶点。
It has been reported that loss of Hugl‐2 contributes to tumour formation and progression in vitro and in vivo. However, whether Hugl‐2 levels decrease during kidney renal clear cell carcinoma (KIRC) and the mechanism involved remain unknown. This study aimed to investigate whether DNA methylation of Hugl‐2 reduces its expression, leading to the progression and poor prognosis of KIRC. Hugl‐2 methylation and mRNA expression and KIRC clinicopathological data were extracted from The Cancer Genome Atlas (TCGA), and relationships among these factors were analyzed using UALCAN, MethHC, Wanderer and LinkedOmics web tools. We found that Hugl‐2 mRNA and protein levels were reduced in KIRC tissues. Moreover, Hugl‐2 mRNA levels were related to tumour grade and overall survival, and Hugl‐2 methylation was increased in KIRC. According to the results of methylation‐specific PCR, KIRC cells had higher Hugl‐2 DNA methylation levels than HKC cells. Moreover, Hugl‐2 DNA methylation correlated negatively with Hugl‐2 mRNA and was also related to the pathology and T stage of KIRC patients. KIRC patients with high Hugl‐2 DNA methylation also had shorter overall survival. Additionally, methylation of cg08827674, a Hugl‐2 probe, was related to pathologic stage, T stage, neoplasm histologic grade, serum calcium level without laterality, M stage, N stage, and ethnicity. Furthermore, treatment with the DNA methylation inhibitor decitabine resulted in upregulation of Hugl‐2 mRNA and protein levels in KIRC cell lines. These results indicate that Hugl‐2 DNA methylation may be both a prognostic marker and a therapeutic target in KIRC.
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影响因子：
4
作者：
Lasseigne BN;Brooks JD
通讯作者：
Brooks JD
DLG5 缺失通过抑制 Hippo 信号通路促进乳腺癌恶性
影响因子：
4.6
作者：
Liu J;Li J;Li P;Wang Y;Liang Z;Jiang Y;Li J;Feng C;Wang R;Chen H;Zhou C;Zhang J;Yang J;Liu P
通讯作者：
Liu P
影响因子：
12.3
作者：
Morris MR;Maher ER
通讯作者：
Maher ER
DOI：
10.1038/nrdp.2017.9
发表时间：
2017-03-09
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Hsieh JJ;Purdue MP;Signoretti S;Swanton C;Albiges L;Schmidinger M;Heng DY;Larkin J;Ficarra V
通讯作者：
Ficarra V
影响因子：
8
作者：
Grifoni, D.;Garoia, F.;Pession, A.
通讯作者：
Pession, A.