Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer
Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer
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DOI：
10.21147/j.issn.1000-9604.2019.05.07
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发表时间：
2019-10-01
影响因子：
5.1
通讯作者：
Xu, Lei
中科院分区：
文献类型：
--
作者：
Huang, Han-Chen;Wen, Xian-Zi;Xu, Lei
目的：胃癌的异质性使得寻找合适的胃癌生物标志物具有挑战性。在这里，我们的目的是确定预后基因GC使用computational analysis.Methods：我们首先使用微阵列技术，从198例胃癌和配对的非肿瘤组织的基因表达谱。基于这些特征和患者的临床信息，我们接下来使用新的计算方法鉴定了预后基因。磷酸葡萄糖异构酶又称葡萄糖-6-磷酸异构酶（GPI），是27个候选基因中的第一个，本研究利用一种新的分析工具--环境基因表型分析（E-GPS）对该酶进行了进一步的研究。GPI作为预后标志物的适用性，其与生理过程，如代谢，上皮间质转化（EMT），以及药物敏感性的关系进行了评估，使用我们自己的和独立的公共datasets.Results：我们发现，GPI在GC中的高表达与患者的生存期延长。特别地，CDH 2和GPI表达的组合有效地分层了TNM II/III期患者的结局。GPI在肿瘤组织中的下调与抑郁的葡萄糖代谢和脂肪酸合成，以及增强脂肪酸氧化和肌酸代谢，表明GPI代表一个合适的标志物增加的可能性EMT在GC cells.Conclusions：我们的研究结果强烈表明，GPI作为一种新的生物标志物候选GC预后，可以大大提高GC患者的临床管理。与GPI相关的潜在代谢重新布线也为研究癌症代谢与患者生存之间的关系提供了新的见解。
Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer (GC) challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients' clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase (GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state (E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition (EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients. Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage II/III. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis, allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.