Department of Colorectal Surgery, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education (Key Laboratory of Molecular Biology in Medical Sciences); The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education (Key Laboratory of Molecular Biology in Medical Sciences); The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Interferon Cytokine Res. 2022 May;42(5):220-234. doi: 10.1089/jir.2021.0214.
Immune-associated biomarkers can predict lung metastases from colorectal cancer. Differentially expressed genes (DEGs) were screened from sample data extracted from gene expression omnibus (GEO) database. The DEGs were screened from the lung metastasis (LM) and primary cancer (PC) groups of the Moffitt Cancer Center cohort dataset. Then, the tumor immune microenvironment and abundance of immune cell infiltration analyses were performed, and the immune-related DEGs were retrieved. In addition, the transcription factor (TF)-miRNA-mRNA network was constructed and enrichment analyses of the immune-related DEGs and upregulated and downregulated DEGs were carried out. Then, the protein-protein interaction (PPI) network was conducted and the drug-gene interaction was predicted. A total of 268 DEGs were screened. The Immune_Score of samples in the LM group was significantly higher compared with the PC group. The infiltration ratio of M0 macrophages and M2 macrophages of samples was higher than others. A total of 54 immune-related DEGs in M0 macrophages were screened. Moreover, the TF-miRNA-mRNA network was constructed among 8 miRNA-mRNA and 50 TF-mRNA, and the secreted phosphoprotein 1 was regulated by 12 TFs, and the oxidized low-density lipoprotein receptor 1 was regulated by 3 miRNAs and 3 TFs. The TF SAM pointed domain containing ETS TF was also a downregulated DEG. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEGs in the TF-miRNA-mRNA network were mainly involved in the interleukin-7 signaling pathway and cell adhesion molecules. In total, 23 protein interactions in this PPI network of M0 macrophage cells were involved in 27 mRNAs. There were 38 drug-gene interactions of immune-related DEGs of M0 macrophage cells predicted to contain 34 small molecule drugs and 8 mRNAs. Finally, the CON cohort dataset verified that the infiltration ratio of M0 and M2 macrophages of the samples was higher.
免疫相关生物标志物可预测结直肠癌的肺转移。从基因表达综合数据库（GEO）数据库中提取的样本数据中筛选差异表达基因（DEGs）。从 Moffitt 癌症中心队列数据集的肺转移（LM）和原发癌（PC）组中筛选 DEGs。然后进行肿瘤免疫微环境和免疫细胞浸润丰度分析，检索与免疫相关的 DEGs。此外，构建转录因子（TF）-miRNA-mRNA 网络，并对免疫相关 DEGs 及上调和下调 DEGs 进行富集分析。然后进行蛋白质-蛋白质相互作用（PPI）网络分析，并预测药物-基因相互作用。共筛选出 268 个 DEGs。LM 组样本的免疫评分明显高于 PC 组。M0 巨噬细胞和 M2 巨噬细胞的样本浸润比例高于其他样本。共筛选出 M0 巨噬细胞中 54 个与免疫相关的 DEGs。此外，构建了 8 个 miRNA-mRNA 和 50 个 TF-mRNA 之间的 TF-miRNA-mRNA 网络，其中分泌磷蛋白 1 受 12 个 TF 调控，氧化型低密度脂蛋白受体 1 受 3 个 miRNA 和 3 个 TF 调控。TF SAM 结构域包含 ETS TF 的转录因子也下调了 DEG。京都基因与基因组百科全书通路分析显示，TF-miRNA-mRNA 网络中的 DEGs 主要参与白细胞介素 7 信号通路和细胞黏附分子。在这个 M0 巨噬细胞 PPI 网络中，共有 23 个蛋白相互作用涉及 27 个 mRNAs。预测 M0 巨噬细胞免疫相关 DEGs 的 38 个药物-基因相互作用包含 34 种小分子药物和 8 个 mRNAs。最后，CON 队列数据集验证了样本中 M0 和 M2 巨噬细胞的浸润比例较高。
