缺氧和免疫抑制的胰腺癌肿瘤微环境中PLAU的表达及对预后的影响

Expression of PLAU in Tumor Microenvironment of Hypoxic and Immunosuppressive Pancreatic Cancer and Its Influence on Prognosis

摘要: 目的：基于生物信息分析，探究PLAU (蛋白编码基因)在以缺氧和免疫抑制为特征的胰腺恶性肿瘤微环境中的表达及其对疾病的进展和预后的影响。方法：通过生物信息分析，使用R语言相关的在线数据库，研究免疫浸润和缺氧在胰腺癌发生发展中的作用，通过Gene ontology (GO)/Kyoto Ency-clopedia of Genes and Genomes (KEGG)富集分析筛选参与调控胰腺癌缺氧和免疫浸润微环境的关键基因；结合UCSC XENA数据库的转录组数据(RNAseq)及随访数据分析对预后的影响；通过ssGSEA算法分析PLAU在胰腺癌免疫细胞中的表达程度和p值；同时，qRT-PCR验证该基因在正常胰腺导管细胞、Panc-1及缺氧环境下培养的Panc-1表达的差异。结果：通过生信分析及GO/KEEG途径，发现PLAU在正常组织和肿瘤组织中的表达有显著差异；根据OS曲线，发现PLAU高表达患者的生存时间明显缩短，单因素COX回归分析发现PLAU、N1期和病理期II期是胰腺癌的独立预后因素，多因素cox回归分析显示，PLAU和N1期是胰腺癌的独立预后因素；PLAU与树突状细胞、巨噬细胞、中性粒细胞、NK CD56dim细胞等免疫细胞浸润程度呈正相关，与Th17细胞浸润程度呈负相关，PLAU高表达组与低表达组相比免疫细胞分布存在差异性；PLAU在胰腺癌细胞中呈高表达，在缺氧的胰腺癌细胞中PLAU的表达低于正常培养的胰腺癌细胞。结论：PLAU在胰腺癌细胞中的差异表达提示其是一种关键的预后基因。它与胰腺癌的缺氧和免疫侵袭有关，在胰腺癌的肿瘤微环境中起重要作用。

Abstract: Objective: Based on bioinformatics analysis, the expression of PLAU (protein coding gene) in the microenvironment of pancreatic malignant tumors characterized by hypoxia and immunosuppres-sion and its impact on disease progression and prognosis were investigated. Methods: The role of immune invasion and hypoxia in the occurrence and development of pancreatic cancer was studied through bioinformatics analysis and R language related online database, and key genes involved in regulating the hypoxia and immune invasion microenvironment of pancreatic cancer were screened through Gene Ontology (GO)/Kyoto Encyclopedia Of Genes and Genomes (KEGG) enrichment analy-sis; Combined with the UCSC XENA RNAseq database and follow-up data, the impact on prognosis was analyzed; The expression and p value of PLAU in pancreatic cancer immune cells were analyzed by ssGSEA algorithm; At the same time, qRT-PCR in vitro was used to verify the difference in the expression of this gene in normal pancreatic duct cells, Panc-1 and Panc-1 cultured in hypoxia en-vironment. Results: Through the bioinformatics analysis and GO/KEEG pathway, it was found that the expression of PLAU in normal and tumor tissues was significantly different; According to the OS curve, the survival time of patients with high PLAU expression was significantly shortened. Single factor COX regression analysis found that PLAU, N1 and pathological stage II were independent prognostic factors of pancreatic cancer, and multivariate cox regression analysis showed that PLAU and N1 were independent prognostic factors of pancreatic cancer; PLAU was positively correlated with the infiltration of dendritic cells, macrophages, neutrophils, NK CD56dim cells and other im-mune cells, and negatively correlated with the infiltration of Th17 cells. The distribution of immune cells in the high expression group of PLAU was different from that in the low expression group; PLAU was highly expressed in pancreatic cancer cells, and the expression of PLAU in hypoxia pan-creatic cancer cells was lower than that in normal pancreatic cancer cells. Conclusion: The differen-tial expression of PLAU in pancreatic cancer cells suggests that PLAU is a key prognostic gene. It is related to hypoxia and immune invasion of pancreatic cancer and plays an important role in the tumor microenvironment of pancreatic cancer.