Li Shan-Shan, Lian Yi-Fan, Huang Yan-Lin, Huang Yue-Hua, Xiao Jian
Department of Medical Oncology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
J Cancer. 2020 Jan 1;11(1):121-131. doi: 10.7150/jca.35763. eCollection 2020.
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.
前胶原赖氨酸2-氧代戊二酸5-双加氧酶（PLODs）是一组参与赖氨酸羟化和通过交联稳定胶原蛋白的酶。先前的研究强调，PLOD基因的过表达与不同人类癌症的进展、迁移和侵袭有关。然而，PLOD基因在胃癌（GC）中的不同表达模式和预后价值仍有待阐明。在本研究中，我们通过ONCOMINE、UALCAN和Kaplan-Meier Plotter数据库挖掘了GC患者的表达和生存数据。使用STRING门户与DAVID相结合，建立PLOD家族基因的功能蛋白相互作用网络，并分析GO和KEGG富集通路。通过LinkedOmics鉴定与PLOD家族基因相关的差异基因表达。我们发现，与正常组织相比，GC患者中PLOD1、2和3上调。PLOD1和PLOD3的高表达水平与总生存期（OS）、首次进展（FP）和进展后生存期（PPS）缩短相关，而PLOD2的高表达水平仅与所有GC患者的较短FP相关。具体而言，仅PLOD2高表达与弥漫型GC患者的较短OS、FP和PPS显著相关。此外，所有PLOD基因表达的联合使用是GC患者的一个更好的预后指标。通路分析证实，PLOD家族基因主要参与调节胶原蛋白代谢和细胞外基质组成，而有助于将细胞外信号转化为细胞内信号的细胞衔接蛋白SHC1可能是介导PLOD对GC作用的调节模块。因此，我们提出单个PLOD基因或整个PLOD家族基因可能是GC的潜在预后生物标志物。
