Overexpressing PLOD family genes predict poor prognosis in gastric cancer
Overexpressing PLOD family genes predict poor prognosis in gastric cancer
复制标题
DOI：
10.7150/jca.35763
复制
发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Xiao, Jian
中科院分区：
文献类型：
--
作者：
Li, Shan-Shan;Lian, Yi-Fan;Xiao, Jian
前胶原-赖氨酸，2-酮戊二酸5-双加氧酶（PLOD）是一组参与赖氨酸羟基化和通过交联稳定胶原的酶。先前的研究已经强调过表达PLOD基因与不同人类癌症的进展、迁移和进展相关。然而，PLOD基因在胃癌（GC）中的多样性表达模式和预后价值仍有待阐明。本研究通过ONCOMINE、UALCAN和Kaplan-Meier Plotter数据库挖掘胃癌患者的表达和生存数据。利用STRING portal和大卫构建PLOD家族基因的功能蛋白相互作用网络，分析GO和KEGG富集通路。用LinkedOmics鉴定与PLOD家族基因相关的差异基因表达。我们发现PLOD 1、2和3在胃癌患者中表达较正常组织中上调。PLOD 1和PLOD 3的高表达水平与较短的总生存期（OS）、首次进展生存期（FP）和进展后生存期（PPS）相关，而PLOD 2的高表达水平仅与较短的FP相关。在弥漫型胃癌患者中，仅PLOD 2高表达与OS、FP和PPS较短显著相关。此外，所有PLOD基因表达的组合使用是GC患者的上级预后指标。通路分析证实PLOD家族基因主要参与调节胶原代谢和细胞外基质的构成，而细胞衔接蛋白SHC 1可能是PLOD对GC作用的调节模块，它有助于将细胞外信号转化为细胞内信号。因此，我们认为单个PLOD基因或PLOD家族基因作为一个整体可能是胃癌潜在的预后生物标志物。
Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a set of enzymes involved in the hydroxylation of lysine and stabilization of collagen by crosslinks. Previous studies have highlighted that overexpressing PLOD genes were related to the progression, migration and progression of different human cancers. However, the diverse expression patterns and prognostic values of PLOD genes remain to be elucidated in gastric cancer (GC). In this study, we mined the expression and survival data in GC patients through ONCOMINE, UALCAN and Kaplan-Meier Plotter database. STRING portal couple with DAVID was used to establish a functional protein interaction network of PLOD family genes and analyze the GO and KEGG enriched pathways. Differential gene expression correlated with PLOD family genes was identified with LinkedOmics. We found that PLOD1, 2 and 3 were up-regulated in GC patients compared with normal tissues. High expression levels of PLOD1 and PLOD3 were associated with shorter overall survival (OS), first progression (FP) and post progression survival (PPS) while high expression level of PLOD2 was only associated with shorter FP in all GC patients. Specifically, only high PLOD2 expression had significant correlation with shorter OS, FP and PPS in the diffuse type GC patients. Furthermore, combinatorial use of expressions of all PLOD genes was a superior prognostic indicator for GC patients. Pathway analysis confirmed that PLOD family genes mainly participate in regulating the collagen metabolism and extracellular matrix constitution, and the cellular adaptor protein SHC1, which helps to transduce an extracellular signal into an intracellular signal, could be the regulatory module mediating PLOD's effect on GC. Therefore, we propose that individual PLOD genes or PLOD family genes as a whole could be potential prognostic biomarkers for GC.