DataSheet_1_The prognostic value and immunological role of angiogenesis-related patterns in colon adenocarcinoma.xlsx

Colon adenocarcinoma (COAD) is a malignant tumor with a high mortality rate. Angiogenesis plays a key role in the development and progression of cancer. However, in COAD, studies between angiogenesis and prognosis, immune cell infiltration, and personalized treatment guidance are currently lacking. In the present study, we comprehensively assessed 35 angiogenesis-related genes (ARG) and identified key ARGs affecting OS in COAD patients. The ARG Prognostic Index (ARGPI) was constructed based on a univariate Cox regression model and its prognostic value was evaluated in TCGA-COAD, GSE39582, GSE161158 and TRSJTUSM Cohort. We constructed ARGPI as an independent risk factor for OS in COAD patients and combined with clinical parameters to further construct an ARGPI-based nomogram, which showed a strong ability to predict overall survival in COAD patients. High ARGPI is associated with cancer-related and immune-related biological processes and signaling pathways; high TP53 mutation rate; high infiltration of MSC, pericytes, and stromal cells; and more CMS4 subtype. And low ARGPI benefited more from immune checkpoint inhibitor treatment. In addition, we also predicted the sensitivity of different ARGPI groups to common chemotherapeutic and targeted agents. In conclusion, this study constructed an ARGPI based on ARG, which robustly predicted the OS of COAD patients and provided a possible personalized treatment regime for COAD patients.

结肠腺癌（Colon adenocarcinoma, COAD）是一种死亡率较高的恶性肿瘤。血管生成在癌症的发生发展进程中发挥关键作用，但目前针对结肠腺癌中血管生成与患者预后、免疫细胞浸润以及个性化治疗指导之间关联的研究仍较为匮乏。本研究对35个血管生成相关基因（angiogenesis-related genes, ARG）进行了全面分析，并筛选出了影响结肠腺癌患者总生存期（overall survival, OS）的关键血管生成相关基因。本研究基于单变量Cox回归模型构建了血管生成相关基因预后指数（ARG Prognostic Index, ARGPI），并在TCGA-COAD队列、GSE39582队列、GSE161158队列以及TRSJTUSM队列中评估了该指数的预后价值。本研究证实ARGPI可作为结肠腺癌患者总生存期的独立危险因素，并结合临床参数进一步构建了基于ARGPI的列线图，该列线图对结肠腺癌患者的总生存期具有优异的预测性能。高ARGPI水平与肿瘤相关及免疫相关的生物学过程、信号通路显著相关，同时伴随较高的TP53突变率、间充质干细胞（MSC）、周细胞及基质细胞的高浸润，以及更高比例的CMS4亚型。低ARGPI水平的患者可从免疫检查点抑制剂治疗中获得更显著的临床获益。此外，本研究还预测了不同ARGPI分组患者对常见化疗药物及靶向药物的敏感性差异。综上，本研究基于血管生成相关基因构建了ARGPI，该指数可稳定且可靠地预测结肠腺癌患者的总生存期，并为结肠腺癌患者提供了潜在的个性化治疗策略。