Guo Zixin, Huang Jingyu, Wang Yujin, Liu Xiao-Ping, Li Wei, Yao Jie, Li Sheng, Hu Weidong
Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Genet. 2020 Jun 12;11:547. doi: 10.3389/fgene.2020.00547. eCollection 2020.
To explore the expression of secreted phosphoprotein 1 (SPP1) in lung adenocarcinoma (LUAD), and evaluate its relationship with clinicopathological characteristics and prognosis of LUAD, and analyze the advantages of SPP1 as a potential prognostic marker in LUAD.
The expression of SPP1 in normal lung tissue and LUAD was analyzed from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA) databases. GSE68465 was used to explore the relationship between the SPP1 expression and clinicopathological characteristics and the prognosis of LUAD patients. The relationship between SPP1 and immune infiltration in LUAD was analyzed by the Tumor Immune Estimation Resource (TIMER) database. Gene enrichment analysis was performed in GSEA. The Cancer Genome Atlas (TCGA)-LUAD data was used to verify the results.
In the cell line level, non-small cell lung cancer ranked ninth among cancer cell lines based on SPP1 expression. In the messenger RNA (mRNA) and protein levels, SPP1 expression was higher in LUAD tissues than that in normal control. SPP1 expression was related to gender, N stage, histological grade, and progression or relapse. In men, SPP1 expression were higher compared to that in women. The higher the N stage, the higher the SPP1 expression level. As LUAD progresses or relapses, SPP1 expression could increase. In the pathological grade, the SPP1 expression was higher in LUAD samples with moderate differentiation. In addition, the overall 5-year survival rates of the SPP1 high and low expression groups were 50.574 and 59.181% [ = 0.008; hazard ratio (HR) = 0.7057; 95% CI, 0.5467-0.9109], indicating that SPP1 had an impact on overall survival for LUAD patients. The relationship between SPP1 expression and CD4 T cell, macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. SPP1 could be considered as an independent prognostic marker in LUAD ( = 0.003; HR = 1.150; 95% CI, 1.048-1.261) by multivariate Cox regression analysis. The results of GSEA indicated that samples with high SPP1 expression were enriched in protein secretion, mTORC1 signaling, angiogenesis, and glycolysis pathway. The analysis results obtained by TCGA-LUAD data were basically consistent with the results obtained by GSE68465.
SPP1 can not only affect the occurrence and development of LUAD but also may be an independent prognostic marker of LUAD. SPP1 is expected to be a new target for molecular targeted therapy.
探讨分泌性磷蛋白1（SPP1）在肺腺癌（LUAD）中的表达，评估其与LUAD临床病理特征及预后的关系，并分析SPP1作为LUAD潜在预后标志物的优势。
从癌症细胞系百科全书（CCLE）、基因表达综合数据库（GEO）和人类蛋白质图谱（HPA）数据库分析SPP1在正常肺组织和LUAD中的表达。使用GSE68465探讨SPP1表达与LUAD患者临床病理特征及预后的关系。通过肿瘤免疫评估资源（TIMER）数据库分析SPP1与LUAD中免疫浸润的关系。在基因集富集分析（GSEA）中进行基因富集分析。使用癌症基因组图谱（TCGA）-LUAD数据验证结果。
在细胞系水平，基于SPP1表达，非小细胞肺癌在癌细胞系中排名第九。在信使核糖核酸（mRNA）和蛋白质水平，LUAD组织中SPP1表达高于正常对照。SPP1表达与性别、N分期、组织学分级及进展或复发有关。在男性中，SPP1表达高于女性。N分期越高，SPP1表达水平越高。随着LUAD进展或复发，SPP1表达可能增加。在病理分级中，中度分化的LUAD样本中SPP1表达较高。此外，SPP1高表达组和低表达组的总体5年生存率分别为50.574%和59.181%[P = 0.008；风险比（HR）= 0.7057；95%置信区间（CI），0.5467 - 0.9109]，表明SPP1对LUAD患者的总生存有影响。在LUAD中，SPP1表达与CD4 T细胞、巨噬细胞、中性粒细胞和树突状细胞浸润的关系较弱。通过多变量Cox回归分析，SPP1可被视为LUAD的独立预后标志物（P = 0.003；HR = 1.150；95% CI，1.048 - 1.261）。GSEA结果表明，SPP1高表达样本在蛋白质分泌、mTORC1信号传导、血管生成和糖酵解途径中富集。TCGA-LUAD数据获得的分析结果与GSE68465获得的结果基本一致。
SPP1不仅可影响LUAD的发生发展，还可能是LUAD的独立预后标志物。SPP1有望成为分子靶向治疗的新靶点。
