Department of Abdominal Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People's Republic of China.
Department of Oncology and Vascular Interventional Therapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People's Republic of China.
Physiol Genomics. 2024 May 1;56(5):367-383. doi: 10.1152/physiolgenomics.00099.2023. Epub 2023 Dec 11.
Members of the interleukin (IL) family are closely linked to cancer development and progression. However, research on the prognosis of colorectal cancer (CRC) related to IL is still lacking. This study investigated new CRC prognostic markers and offered new insights for CRC prognosis and treatment. CRC-related data and IL gene data were collected from public databases. Sample clustering was done with the NMF package to divide samples into different subtypes. Differential, enrichment, survival, and immune analyses were conducted on subtypes. A prognostic model was constructed using regression analysis. Drug sensitivity analysis was performed using GDSC database. Western blot analysis was performed to assess the effect of IL-7 on the JAK/STAT signaling pathway. Flow cytometry was used to examine the impact of IL-7 on CD8 T cell apoptosis. Two CRC subtypes based on IL-associated genes were obtained. had a higher survival rate than , and they showed differences in some immune levels. The two clusters were mainly enriched in the JAK-STAT signaling pathway, T helper 17 cell differentiation, and the IL-17 signaling pathway. An 11-gene signature was built, and risk score was an independent prognosticator for CRC. The low-risk group showed a higher sensitivity to nine common targeted anticancer drugs. Western blot and flow cytometry results demonstrated that IL-7 could phosphorylate STAT5 and promote survival of CD8 T cells. In conclusion, this study divided CRC samples into two IL-associated subtypes and obtained an 11-gene signature. In addition, targeted drugs that may improve the prognosis of patients with CRC were identified. These findings are of paramount importance for patient prognosis and CRC treatment. We identified two clusters with significant survival differences in colorectal cancer (CRC) based on interleukin-related genes, constructed an 11-gene risk score model that can independently predict the prognosis of CRC, and explored some targeted drugs that may improve the prognosis of patients with CRC. The results of this study have important implications for the prognosis and treatment of CRC.
白细胞介素(IL)家族成员与癌症的发生和发展密切相关。然而,关于与白细胞介素相关的结直肠癌(CRC)预后的研究仍然缺乏。本研究旨在寻找新的 CRC 预后标志物,并为 CRC 的预后和治疗提供新的思路。从公共数据库中收集与 CRC 相关的数据和 IL 基因数据。使用 NMF 包对样本进行聚类,将样本分为不同的亚型。对亚组进行差异分析、富集分析、生存分析和免疫分析。使用回归分析构建预后模型。使用 GDSC 数据库进行药物敏感性分析。使用 Western blot 分析评估 IL-7 对 JAK/STAT 信号通路的影响。使用流式细胞术检测 IL-7 对 CD8 T 细胞凋亡的影响。基于与 IL 相关的基因获得了两种 CRC 亚型。亚型 具有更高的生存率,并且在某些免疫水平上存在差异。这两个聚类主要富集在 JAK-STAT 信号通路、辅助性 T 细胞 17 分化和 IL-17 信号通路中。构建了一个 11 基因特征,风险评分是 CRC 的独立预后因素。低风险组对九种常见的靶向抗癌药物表现出更高的敏感性。Western blot 和流式细胞术结果表明,IL-7 可以磷酸化 STAT5 并促进 CD8 T 细胞的存活。总之,本研究根据白细胞介素相关基因将 CRC 样本分为两种亚型,并获得了一个 11 基因的风险评分模型。此外,还确定了一些可能改善 CRC 患者预后的靶向药物。这些发现对患者的预后和 CRC 的治疗具有重要意义。我们基于白细胞介素相关基因鉴定了两种具有显著生存差异的结直肠癌(CRC)亚群,构建了一个能够独立预测 CRC 预后的 11 基因风险评分模型,并探索了一些可能改善 CRC 患者预后的靶向药物。本研究的结果对 CRC 的预后和治疗具有重要意义。