Second Clinical Medical College, Lanzhou University, Lanzhou, China.
Department of Cancer Center, Lanzhou University Second Hospital, Lanzhou, China.
Front Immunol. 2022 Nov 30;13:1023908. doi: 10.3389/fimmu.2022.1023908. eCollection 2022.
Colorectal cancer (CRC) is a common cancer and has a poor prognosis. The coagulation system and fibrinolysis system are closely related to the progression of malignant tumors and is also related to the immunotherapy of malignant tumors. Herein, we tried to predict survival and the immunotherapy effect for patients with CRC using a novel potential prognostic model.
Through online data of TCGA and GEO, we screened significantly differentially expressed genes (DEGs) to construct a prognostic model, followed by obtaining immune-related genes (IRGs) from the ImmPort database and coagulation- and fibrinolysis-related genes (CFRGs) from the GeneCards database. The predictive power of the model is assessed by Kaplan-Meier survival curves as well as the time-dependent ROC curve. Moreover, univariate and multivariate analyses were conducted for OS using Cox regression models, and the nomogram prognostic model was built. In the end, we further studied the possibility that CXCL8 was associated with immunocyte infiltration or immunotherapy effect and identified it by immunohistochemistry and Western blot.
Five DEGs (CXCL8, MMP12, GDF15, SPP1, and NR3C2) were identified as being prognostic for CRC and were selected to establish the prognostic model. Expression of these genes was confirmed in CRC samples using RT-qPCR. Notably, those selected genes, both CFRGs and IRGs, can accurately predict the OS of CRC patients. Furthermore, CXCL8 is highly correlated with the tumor microenvironment and immunotherapy response in CRC.
Overall, our established IRGPI can very accurately predict the OS of CRC patients. CXCL8 reflects the immune microenvironment and reveals the correlation with immune checkpoints among CRC patients.
结直肠癌（CRC）是一种常见的癌症，预后较差。凝血系统和纤溶系统与恶性肿瘤的进展密切相关，也与恶性肿瘤的免疫治疗有关。在此，我们试图使用一种新的潜在预后模型来预测 CRC 患者的生存和免疫治疗效果。
通过在线 TCGA 和 GEO 数据，我们筛选出显著差异表达基因（DEGs）来构建预后模型，然后从 ImmPort 数据库中获得免疫相关基因（IRGs），从 GeneCards 数据库中获得凝血和纤溶相关基因（CFRGs）。通过 Kaplan-Meier 生存曲线和时间依赖性 ROC 曲线评估模型的预测能力。此外，使用 Cox 回归模型对 OS 进行单因素和多因素分析，并构建列线图预后模型。最后，我们进一步研究了 CXCL8 与免疫细胞浸润或免疫治疗效果相关的可能性，并通过免疫组化和 Western blot 进行了鉴定。
鉴定出 5 个 DEGs（CXCL8、MMP12、GDF15、SPP1 和 NR3C2）与 CRC 的预后相关，并被选来建立预后模型。使用 RT-qPCR 验证了这些基因在 CRC 样本中的表达。值得注意的是，这些选定的基因，包括 CFRGs 和 IRGs，都可以准确地预测 CRC 患者的 OS。此外，CXCL8 与 CRC 中的肿瘤微环境和免疫治疗反应高度相关。
总之，我们建立的 IRGPI 可以非常准确地预测 CRC 患者的 OS。CXCL8 反映了肿瘤微环境，并揭示了 CRC 患者中与免疫检查点的相关性。
