目的通过高通量测序研究肺腺癌合并肺栓塞及肺栓塞患者基因表达谱数据，应用生物信息学方法挖掘肺腺癌合并肺栓塞及肺栓塞患者的共同信号通路，筛选两对比组共同的差异mRNA。
方法收集新疆医科大学附属肿瘤医院2019年1月至2019年12月肺腺癌合并肺栓塞、单纯肺腺癌、单纯肺栓塞及健康体检者外周血(每组4例，共计16例)，采用RNA测序技术检测16例入组人群的基因表达谱数据，将肺腺癌合并肺栓塞组与单纯肺腺癌组基因表达谱数据作为一个数据集，单纯肺栓塞组及健康对照组的基因表达数据为另一个数据集。经R语言筛选两数据集的差异表达基因，并经Excel软件取交集，获得两对比组共同差异mRNA。并通过基因本体(GO)注释分析、京都基因与基因组百科全书(KEGG)信号通路分析筛选两对比组共同的功能聚类及信号通路。
结果肺腺癌合并肺栓塞组对比肺腺癌组、肺栓塞组对比健康对照组的共同差异mRNA有14个，其中上调10个，下调4个，差异最明显的下调mRNA是溶质载体家族9成员3(SLC9A3)；GO分析表明两对比组均与细胞生物过程、补体反应、炎性反应等相关，KEGG通路分析表明两对比组的共同富集的通路包括补体和凝血级联、系统性红斑狼疮、类风湿性关节炎、核因子-κB(NF-κB)信号通路等。
结论显著下调的差异mRNA SLC9A3或可作为肺腺癌合并肺栓塞的生物标志物。肺腺癌合并肺栓塞的发生可能涉及补体反应、炎性反应等分子功能，也可能与补体和凝血级联、系统性红斑狼疮、类风湿性关节炎、NF-κB信号通路等相关。
ObjectiveUsing high-throughput sequencing to investigate the gene expression profile data of patients with lung adenocarcinoma complicated with pulmonary embolism and pulmonary embolism. Bioinformatics was used to mine the common signal pathway of patients with lung adenocarcinoma complicated with pulmonary embolism and pulmonary embolism to screen the differentially expressed mRNAs between the two contrast groups.
MethodsThe peripheral blood of patients with lung adenocarcinoma complicated with pulmonary embolism, lung adenocarcinoma, pulmonary embolism and healthy subjects (4 cases in each group , with a total of 16 cases) were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January to December 2019. The gene expression profile data sets of 16 cases in the group were constructed by RNA sequencing. One data set is the gene expression profile data of lung adenocarcinoma with pulmonary embolism group and lung adenocarcinoma group, and the other is the gene expression data of pulmonary embolism group and healthy control group. The differentially expressed genes of the two data sets were screened by R language, and the common differential mRNA of the two contrast groups was screened by the intersection of the two data sets by Excel software.The functional clustering and enriched signal pathways of the two contrast groups were screened by GO analysis and kyoto encyclopedia of genes and genomes (KEGG) signal pathway analysis.
ResultsThere were 14 common differentially expressed mRNAs between lung adenocarcinoma complicated with pulmonary embolism group and pulmonary embolism group and between pulmonary embolism group and healthy control group, of which including 10 up-regulated mRNAs and 4 down-regulated mRNAs. The most significantly down-regulated mRNA was solute carrier family 9 member 3 (SLC9A3). The GO analysis showed that the two contrast groups were related to cellular biological process, complement response and inflammatory response. The KEGG pathway analysis showed that the common enriched pathways in the two contrast groups included complement and coagulation cascade, systemic lupus erythematosus, rheumatoid arthritis, nuclear factor-κB (NF-κB) signal pathway and so on.
ConclusionThe SLC9A3 may be used as a biomarker of lung adenocarcinoma with pulmonary embolism. The occurrence of pulmonary embolism in lung adenocarcinoma may be related to complement response, inflammatory response and other molecular functions, and may also be related to complement and coagulation cascade, systemic lupus erythematosus, rheumatoid arthritis, nuclear factor-κB (NF-κB) signal pathway and so on.
王清鹤,曹国磊,张秀华,等. 肺腺癌合并肺栓塞患者的差异mRNA表达分析[J]. 中华实验外科杂志,2020,37(06)：1145-1148.
DOI:10.3760/cma.j.cn421213-20191217-01543版权归中华医学会所有。
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