Zhang Chen, Liu Tao, Yun Zhennan, Liang Bin, Li Xue, Zhang Jiantao
Colorectal and Anal Surgery Department, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China.
Front Pharmacol. 2023 Feb 22;14:1103547. doi: 10.3389/fphar.2023.1103547. eCollection 2023.
Angiogenesis is one of the most prominent markers of cancer progression and contributes to tumor metastasis and prognosis. Anti-angiogenic drugs have proven effective in treating metastatic colorectal cancer. However, there is some uncertainty regarding the potential role of angiogenesis-related genes in the tumor microenvironment. We analyzed 1,214 colorectal cancer samples to identify alterations in angiogenesis-related genes (ARGs), and then correlated angiogenesis with clinical features, prognosis, and TME. The ARGs expression profiles in colorectal cancer were analyzed using three computational methods (CIBERSORT, ssGSEA, and MCPcounter) and provided a systematic immune landscape. Patients with CRC were classified into two subtypes based on consensus clustering analysis of angiogenesis-related genes. The revealed differentially expressed genes between the two subtypes were used to create and validate ARGscore prognostic models. In addition, we collected eight colorectal cancer patient specimens and performed RT-qPCR to validate the signature gene expression. We assessed the expression patterns of ARGs in colorectal cancer. We identified two molecular subtypes and confirmed that the expression of ARGs was associated with prognosis and TME characteristics. Based on differentially expressed genes between subtypes, we constructed ARGscore and evaluated their predictive power for the survival of colorectal cancer patients. We also developed an accurate nomogram to make the ARGscore more clinically useful. In addition, ARGscore was significantly correlated with microsatellite instability, cancer stem cells, and chemotherapeutic drug sensitivity. Patients with ARGscore-low characterized by immune activation and microsatellite instability high had a better prognosis. ARGs expression influenced the prognosis, clinicopathological features, and tumor stromal immune microenvironment in colorectal cancer. We developed a new risk model, ARGscore, for the treatment and prognosis of CRC patients and validated its promising predictive power. These findings will enable us to understand colorectal cancer better, assess prognoses, and develop more effective treatment options.
血管生成是癌症进展最显著的标志物之一，有助于肿瘤转移和预后。抗血管生成药物已被证明对治疗转移性结直肠癌有效。然而，血管生成相关基因在肿瘤微环境中的潜在作用仍存在一些不确定性。我们分析了1214例结直肠癌样本，以确定血管生成相关基因（ARGs）的改变，然后将血管生成与临床特征、预后和肿瘤微环境进行关联。使用三种计算方法（CIBERSORT、ssGSEA和MCPcounter）分析了结直肠癌中ARGs的表达谱，并提供了一个系统的免疫图谱。基于血管生成相关基因的共识聚类分析，将结直肠癌患者分为两个亚型。利用两个亚型之间差异表达的基因创建并验证了ARGscore预后模型。此外，我们收集了8例结直肠癌患者标本并进行RT-qPCR以验证特征基因的表达。我们评估了结直肠癌中ARGs的表达模式。我们鉴定出两个分子亚型，并证实ARGs的表达与预后和肿瘤微环境特征相关。基于亚型之间的差异表达基因，我们构建了ARGscore并评估了它们对结直肠癌患者生存的预测能力。我们还开发了一个准确的列线图，使ARGscore在临床上更有用。此外，ARGscore与微卫星不稳定性、癌症干细胞和化疗药物敏感性显著相关。以免疫激活和高微卫星不稳定性为特征的低ARGscore患者预后较好。ARGs的表达影响了结直肠癌的预后、临床病理特征和肿瘤基质免疫微环境。我们开发了一种新的风险模型ARGscore，用于结直肠癌患者的治疗和预后评估，并验证了其有前景的预测能力。这些发现将使我们能够更好地理解结直肠癌，评估预后，并开发更有效的治疗方案。
