背景:前胶原-赖氨酸,2-酮戊二酸5-双加氧酶(PLOD)是一组可以介导赖氨酰羟化为羟赖氨酸并参与稳定胶原蛋白形成的酶。有证据表明,PLOD参与了肿瘤进展的步骤,包括扩散,入侵,和转移。然而,关于PLOD1/2/3在肺癌中的功能的信息有限.在这项研究中,我们研究了PLODs在肺腺癌(LUAD)和肺鳞癌(LUSC)患者中的表达模式和预后价值.
方法:使用Oncomine数据库和UALCAN分析非小细胞肺癌(NSCLC)中PLOD家族成员的mRNA表达水平。通过Kaplan-Meier绘图仪数据库研究了PLOD的预后价值。我们搜集33例肺癌患者进一步验证PLODs的表达谱和预后价值。使用Kaplan-Meier方法进行生存曲线,并进行对数秩检验以评估生存率的差异。根据GSE31210的数据集,我们进行了单因素和多因素分析,以确定PLOD是否是生存的独立预后指标.同时,我们调查了突变,基于cBioPortal的PLOD的潜在生物学功能和免疫相关性,分别为Metascape和TIMER数据库。
结果:我们发现NSCLC组织中PLODs的mRNA和蛋白表达水平高于正常肺组织。PLOD1/2/3的高表达与LUAD的低生存率显著相关,但与LUSC无关。此外,GSE31210数据集显示,PLOD1和PLOD3是LUAD患者无复发生存期和总生存期(OS)的独立危险因素.我们观察到LUSC患者的PLODs改变率很高,PLOD的遗传改变与有利OS显著相关。此外,我们观察到PLODs与肺癌的肿瘤免疫显著相关.对京都基因和基因组百科全书(KEGG)途径的富集分析表明,PLODs的功能集中在细胞周期上,DNA复制,和LUAD的糖酵解/糖异生。
结论:这些结果表明PLODs在肺癌中高表达,可能是合适的预后标志物。
BACKGROUND: Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a group of enzymes that can mediate the hydroxylation of lysyl to hydroxylysine and participate in the formation of stabilized collagen. Evidence has demonstrated that PLODs are involved in the steps of tumor progression, including proliferation, invasion, and metastasis. However, limited information is available on the function of PLOD1/2/3 in lung cancer. In this study, we investigated the expression patterns and prognostic values of PLODs in patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).
METHODS: The Oncomine database and UALCAN were used to analyze the mRNA expression levels of PLOD family members in non-small cell lung cancer (NSCLC). The prognostic values of PLODs were investigated by the Kaplan-Meier Plotter database. We collected 33 patients with lung cancer to further verify the expression profiles and prognostic values of PLODs. The Kaplan-Meier method was used to perform survival curves, and the log-rank test was performed to evaluate the differences in survival. According to the GSE31210 databset, univariate and multivariate analyses were performed to identify whether PLODs were independent prognostic indicators for survival. Meanwhile, we investigated the mutations, potential biological functions and immune relevance of PLODs on the basis of the cBioPortal, Metascape and TIMER databases respectively.
RESULTS: We found that the mRNA and protein expression levels of PLODs in NSCLC tissues were higher than those in normal lung tissues. High PLOD1/2/3 expression had significant relevance to poor survival in LUAD but not in LUSC. In addition, the GSE31210 dataset showed that PLOD1 and PLOD3 were independent risk factors for relapse-free survival and overall survival (OS) in LUAD. We observed a high alteration rate of PLODs in LUSC patients, and the genetic alterations of PLODs had significant relevance to favorable OS. Furthermore, we observed that PLODs were significantly associated with tumor immunity in lung cancer. The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the functions of the PLODs focused on cell cycle, DNA replication, and glycolysis/gluconeogenesis in LUAD.
CONCLUSIONS: These results indicated that PLODs were highly expressed in lung cancer and may be suitable prognostic markers.