基于生物信息学分析LMNB2在胃癌中的表达及其与肿瘤微环境的关系

Expressions of LMNB2 expression in gastric cancer and its rolelationship with the in tumor microenvironment based on bioinformatics analysis

目的:近年来,肿瘤微环境在恶性肿瘤中的作用受到广泛关注,但胃癌与肿瘤微环境的关系尚不完全清楚。本研究旨在探讨核纤层蛋白B2(nuclear lamina protein B2,LMNB2)在胃癌中的表达及其与肿瘤微环境的关系。方法:通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)分析LMNB2基因在胃癌组织及正常胃黏膜组织中的表达差异。收集92例手术切除的胃癌及相应癌旁5 cm以上的胃黏膜组织标本,采用免疫组织化学方法检测其中LMNB2的表达情况,并分析LMNB2的表达水平与胃癌患者临床病理特征之间的关系。运用Kaplan-Meier生存曲线分析LMNB2表达水平与胃癌生存预后的关系。通过R软件和TISIDB(an integrated repository portal for tumor-immune system interactions)数据库对目标基因进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,并分析其与肿瘤免疫特征之间的相关性。基于CIBERSORT(Cell-type Identification by Estimating Relative Subsets of RNA Transcripts)算法进行LMNB2表达与免疫细胞浸润水平相关性预测,评价LMNB2表达水平对肿瘤微环境的影响。结果:TCGA数据库分析显示:胃癌组织中的LMNB2基因表达水平较正常胃黏膜组织明显增高(P<0.001)。LMNB2的表达水平与胃癌患者的淋巴结转移、肿瘤浸润深度、TNM分期及远处转移均有关(均P<0.05),与患者性别、年龄、肿瘤大小等无关(均P>0.05)。Kaplan-Meier生存曲线显示:LMNB2表达阳性患者总体生存时间较LMNB2阴性患者显著缩短(P<0.001)。LMNB2差异基因主要集中富集在体液免疫反应的调节等过程。此外LMNB2差异基因的表达与M0型巨噬细胞、CD4^(+)记忆T细胞等免疫细胞浸润水平均呈正相关(均P<0.05)。结论:LMNB2在胃癌组织中呈高表达,与患者预后生存不良相关,LMNB2与胃癌预后和免疫微环境高度相关,有望成为胃癌免疫治疗的潜在生物标志物。

Objective:In recent years,the role of tumor microenvironment in malignanciest tumors has been widespread attentionly concerned in recent years,but the relationship between gastric cancer and tumor microenvironment is not completely clear.This study aims to explore the expression of nuclear lamina protein B2(LMNB2)in gastric cancer and its relationship with the tumor microenvironment.Methods:The Cancer Genome Atlas(TCGA)was used to analyze the differences in LMNB2 expression between gastric cancer tissues and normal tissues.Samples from 92 cases of surgically resected gastric cancer and non-cancerous gastric mucosa tissues(more than 5 cm away from the tumor)adjacent to the corresponding cancer were collected.Immunohistochemistry was employed to detect LMNB2 expression and analyze its association with clinicopathological characteristics in gastric cancer patients.Kaplan-Meier survival curves were used to analyze the relationship between LMNB2 expression levels and the survival and prognosis of patients with gastric cancer.The enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed so as to explore the correlation between the target genes and tumor immune characteristics by R software and the TISIDB(an integrated repository portal for tumor-immune system interactions)database.The CIBERSORT(Cell-type Identification by Estimating Relative Subsets of RNA Transcripts)algorithm was used to predict the correlation between LMNB2 expression and immune cell infiltration levels,evaluating the influence of LMNB2 expression level on the tumor microenvironment.Results:TCGA database analysis showed that LMNB2 expression levels in gastric cancer tissues was significantly higher than that in the normal gastric mucosa tissues(P<0.001).The expression level of LMNB2 was related with lymph node metastasis,tumor infiltration depth of tumor invasion,TNM stageing and distant metastasis in patients with gastric cancer patients(all P<0.05),but not with age,gender,age,or tumor size(all P>0.05).Kaplan-Meier survival curves showed that the LMNB2 positive expression patients had significantly shorter overall survival times compared to the LMNB2 negative expression patients(P<0.001).LMNB2 differentially expressed genes were primarimainly enriched in the regulation proccess of humoral immune response.Additionally,the expression of LMNB2 differential expression gene was positively correlated with the infiltration levels of immune cells,including M0 macrophages,CD4^(+)memory T cells,and other immune cells(all P<0.05).Conclusion:LMNB2 is highly expressed in gastric cancer tissues,which is related to the poor prognosis and survival in patients.LMNB2 expression is highly related with the prognosis and immune microenvironment of gastric cancer,and which is expected to become a potential biomarker for immunotherapy of gastric cancer.