Department of Rheumatology and Immunology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China.
BMC Cancer. 2021 Mar 10;21(1):259. doi: 10.1186/s12885-021-07959-6.
The incidence and mortality of lung cancer are the highest among all cancers. Patients with systemic sclerosis show a four-fold greater risk of lung cancer than the general population. However, the underlying mechanism remains poorly understood.
The expression profiles of 355 peripheral blood samples were integratedly analyzed, including 70 cases of lung cancer, 61 cases of systemic sclerosis, and 224 healthy controls. After data normalization and cleaning, differentially expressed genes (DEGs) between disease and control were obtained and deeply analyzed by bioinformatics methods. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed online by DAVID and KOBAS. The protein-protein interaction (PPI) networks were constructed from the STRING database.
From a total of 14,191 human genes, 299 and 1644 genes were identified as DEGs in systemic sclerosis and lung cancer, respectively. Among them, 64 DEGs were overlapping, including 36 co-upregulated, 10 co-downregulated, and 18 counter-regulated DEGs. Functional and enrichment analysis showed that the two diseases had common changes in immune-related genes. The expression of innate immune response and response to virus-related genes increased significantly, while the expression of negative regulation of cell cycle-related genes decreased notably. In contrast, the expression of mitophagy regulation, chromatin binding and fatty acid metabolism-related genes showed distinct trends.
Stable differences and similarities between systemic sclerosis and lung cancer were revealed. In peripheral blood, enhanced innate immunity and weakened negative regulation of cell cycle may be the common mechanisms of the two diseases, which may be associated with the high risk of lung cancer in systemic sclerosis patients. On the other hand, the counter-regulated DEGs can be used as novelbiomarkers of pulmonary diseases. In addition, fat metabolism-related DEGs were consideredto be associated with clinical blood lipid data.
肺癌的发病率和死亡率在所有癌症中最高。系统性硬化症患者患肺癌的风险比普通人群高四倍。然而，其潜在机制仍知之甚少。
综合分析了 355 份外周血样本的表达谱，包括 70 例肺癌、61 例系统性硬化症和 224 例健康对照。经过数据归一化和清洗，获得了疾病与对照之间的差异表达基因（DEGs），并通过生物信息学方法进行了深入分析。GO 和 KEGG 通路富集分析在线通过 DAVID 和 KOBAS 进行。从 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络。
在总共 14191 个人类基因中，系统性硬化症和肺癌分别鉴定出 299 和 1644 个 DEGs。其中，有 64 个 DEGs 重叠，包括 36 个共同上调、10 个共同下调和 18 个反向调控 DEGs。功能和富集分析表明，两种疾病的免疫相关基因有共同的变化。先天免疫反应和对病毒反应相关基因的表达显著增加，而细胞周期负调控相关基因的表达显著降低。相比之下，细胞自噬调控、染色质结合和脂肪酸代谢相关基因的表达则呈现出明显的趋势。
揭示了系统性硬化症和肺癌之间存在稳定的差异和相似之处。在外周血中，增强的先天免疫和减弱的细胞周期负调控可能是两种疾病的共同机制，这可能与系统性硬化症患者患肺癌的高风险有关。另一方面，反向调控的 DEGs 可以作为肺部疾病的新型生物标志物。此外，与临床血脂数据相关的脂肪代谢相关 DEGs 被认为与这些数据有关。
