Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer.
Mining distinct aldehyde dehydrogenase 1 (ALDH1) isoenzymes in gastric cancer.
复制标题
挖掘胃癌中不同的乙醛脱氢酶 1 (ALDH1) 同工酶。
DOI：
10.18632/oncotarget.8294
复制
发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Wu HT
中科院分区：
文献类型：
--
作者：
Shen JX;Liu J;Li GW;Huang YT;Wu HT
乙醛脱氢酶1(ALDH1)是一个胞内酶家族，在白血病和一些实体瘤的干细胞群中高度表达。到目前为止，已有6种ALDH1亚型被报道。然而，影响ALDH1活性的ALDH1同工酶的表达模式和同工酶的特性，以及ALDH1同工酶在癌症中的预后价值仍有待阐明。在这里，我们使用Oncomine数据库研究了ALDH1转录本在胃癌(GC)和正常对照中的表达。通过Kaplan-Meier绘图仪数据库，我们还研究了ALDH1同工酶在GC患者中的预后价值。结果发现，与正常组织相比，胃癌组织中ALDH1A1基因表达下调，而ALDH1A3和ALDH1B1基因表达上调。在生存分析中，在所有GC患者中，ALDH1A1和ALDH1B1的高表达与更好的总体生存(OS)相关。此外，ALDH1A1的高转录活性预示着胃肠型腺癌有更好的OS，而在弥漫性胃腺癌中则不是。ALDH1B1基因高表达的胃癌患者胃肠型预后较好，弥漫型预后较差。相反，ALDH1A2、ALDH1A3和ALDH1L1的高转录活性预示着GC患者的总体生存恶化，提示这些同工酶可能是GC中ALDH1活性的主要原因。这些数据提供了ALDH1A2、ALDH1A3和ALDH1L1作为GC患者个体化治疗的良好潜在靶点。
Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database. Through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information of 876 GC patients, we also investigated the prognostic values of ALDH1 isoenzymes in GC patients. It was found that when compared with normal tissues, ALDH1A1 mRNA expression was downregulated, whereas ALDH1A3 and ALDH1B1 were upregulated in GC patients. In survival analyses, high ALDH1A1 and ALDH1B1 expressions were associated with better overall survival (OS) in all GC patients. In addition, high transcription activity of ALDH1A1 predicted better OS in gastric intestinal type adenocarcinoma, but not in diffuse gastric adenocarcinoma. GC patients with high mRNA level of ALDH1B1 showed better OS in gastric intestinal type, and worse OS in diffuse type. Oppositely, high transcription activities of ALDH1A2, ALDH1A3 and ALDH1L1 predicted worsen overall survival in GC patients, suggesting that these isoenzymes might be responsible mainly for the ALDH1 activities in GC. These data provides ALDH1A2, ALDH1A3 and ALDH1L1 as excellent potential targets for individualized treatment of GC patients.
登录
查看更多内容
影响因子：
3.8
作者：
Li XS;Xu Q;Fu XY;Luo WS
通讯作者：
Luo WS
影响因子：
5.1
作者：
Moreb, Jan S.;Ucar, Deniz;Han, Shuhong;Amory, John K.;Goldstein, Alex S.;Ostmark, Blanca;Chang, Lung-Ji
通讯作者：
Chang, Lung-Ji
影响因子：
11.2
作者：
Kim, H;Lapointe, J;Pollack, JR
通讯作者：
Pollack, JR
影响因子：
8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Rhodes, DR;Yu, JJ;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM