Abstract: Objective To investigate the expression and clinicopathological significance of baculoviral inhibitor of apoptosis repeat-containing protein 5 （BIRC5） in lung adenocarcinoma （LUAD） tissue. Methods The expression of BIRC5 mRNA in LUAD and non-cancer lung tissues was collected from high-throughput datasets such as ArrayExpress, GEO, Oncomine, TCGA, and GTEx. SMD and AUC of the sROC cure were calculated; Kaplan-Meier curves were used for the study Association between BIRC5 expression and prognosis in LUAD patients; BIRC5 protein expression level was detected by immunohistochemistry using LUAD tissue microarray. BIRC5-related up-regulated genes were subjected to GO functional annotation, GSEA, and the KEGG signaling pathway analysis. The CIBERCORT algorithm was used to explore the relationship between BIRC5 expression and the immune microenvironment of LUAD. Results A total of 114 high-throughput datasets were included globally, from 22 countries or regions, including 3897 cases of LUAD and 2993 non cancerous lung tissues, and finally merged into 37 platforms. Compared with non cancerous lung tissue, the expression level of BIRC5 mRNA was significantly increased in LUAD tissue （SMD=1.36, AUC=0.90）; The overall survival of LUAD patients with high expression of BIRC5 was significantly lower than those with low expression （hazard ratio=2.017, P<0.05）; At the same time, some experiments on tissue chips found that the expression level of BIRC5 protein was significantly upregulated in 226 cases of LUAD （P<0.05）. The BIRC5 related genes in LUAD may be involved in the formation of cellular components such as chromosomes, involving biological processes such as DNA replication, nuclear division, and chromosome separation, and exerting molecular functions such as ATPase activity and DNA helicase activity. In addition, the high expression group of BIRC5 had a higher level of immune cell infiltration （P<0.05）. Conclusion High expression of BIRC5 may promote the occurrence and progression of LUAD through multiple pathways and immune factors.

Key words: BIRC5, lung adenocarcinoma, tissue chip, prognosis

摘要： 目的 探讨BIRC5在LUAD组织中的表达及其临床病理意义。方法 收集GEO、TCGA,以及GTEx等高通量数据集中的BIRC5 mRNA在LUAD和非癌肺组织中的表达数据,计算SMD及sROC的AUC;使用Kaplan-Meier曲线研究BIRC5表达和LUAD患者预后的关联;使用LUAD组织芯片进行免疫组织化学检测BIRC5蛋白表达水平。在高通量数据集中,对BIRC5相关的上调基因进行GO功能注释,GSEA,以及KEGG信号通路分析。使用CIBERCORT算法探究BIRC5表达与LUAD的免疫微环境的关系。结果 全球范围内,共纳入114个高通量数据集,分别来自22个国家或地区,包含3897例LUAD和2993非癌肺组织,最后合并为37个平台。与非癌肺组织相比,BIRC5 mRNA在LUAD组织中表达水平显著升高（SMD=1.36,AUC=0.90）;高表达BIRC5的LUAD患者的总体生存期显著低于低表达者（hazard ratio=2.017,P<0.05）;同时,组织芯片部分实验发现226例LUAD中BIRC5蛋白水平显著表达上调（P<0.05）。LUAD中BIRC5相关基因可能参与构成染色体等细胞成分,涉及DNA复制、细胞核分裂及染色体分离等生物学过程,并发挥ATP酶活性以及DNA解旋酶活性等分子功能。此外,BIRC5高表达组具有更高的免疫细胞浸润水平（P<0.05）。结论 高表达的BIRC5可能通过多个通路和免疫因素发挥促进LUAD的发生和进展。

关键词: BIRC5, 肺腺癌, 组织芯片, 预后