Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Aging (Albany NY). 2021 Dec 13;13(23):25518-25549. doi: 10.18632/aging.203771.
Globally, colorectal cancer (CRC) is one of the most lethal malignant diseases. However, the currently approved therapeutic options for CRC failed to acquire satisfactory treatment efficacy. Tailoring therapeutic strategies for CRC individuals can provide new insights into personalized prediction approaches and thus maximize clinical benefits.
In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of CRC from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive therapeutics screening to identify agents with subclass-specific efficacy.
The established signature was shown to be a promising biomarker for evaluating clinical outcomes in CRC. The immune risk score as calculated by this classifier was significantly correlated with over-riding malignant phenotypes and immunophenotypes. Further analyses demonstrated that CRCs with low immune risk scores achieved better therapeutic benefits from immunotherapy, while AZD4547, Cytochalasin B and S-crizotinib might have potential therapeutic implications in the immune risk score-high CRCs.
Overall, this IRGs-based signature not only afforded a useful tool for determining the prognosis and evaluating the TIME features of CRCs, but also shed new light on tailoring CRCs with precise treatment.
在全球范围内，结直肠癌（CRC）是最致命的恶性疾病之一。然而，目前批准的 CRC 治疗方案未能获得令人满意的治疗效果。为 CRC 个体定制治疗策略可以为个性化预测方法提供新的见解，从而最大限度地提高临床获益。
在这项研究中，我们利用来自基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库的 CRC 表达谱和临床特征，采用多步骤流程构建了一个基于免疫相关基因（IRG）的签名。我们进行了综合免疫基因组分析，以确定具有预后意义的 IRG 与肿瘤免疫微环境（TIME）中癌症基因型之间的关联。此外，我们进行了全面的治疗筛选，以确定具有亚类特异性疗效的药物。
所建立的签名被证明是评估 CRC 临床结局的有前途的生物标志物。通过该分类器计算的免疫风险评分与主要恶性表型和免疫表型显著相关。进一步的分析表明，免疫风险评分低的 CRC 从免疫治疗中获得更好的治疗效果，而 AZD4547、细胞松弛素 B 和 S-crizotinib 可能对免疫风险评分高的 CRC 具有潜在的治疗意义。
总之，该基于 IRG 的签名不仅为确定 CRC 的预后和评估 TIME 特征提供了有用的工具，而且为精确治疗 CRC 提供了新的思路。
