Li Jianxin, Han Ting, Wang Xin, Wang Yinchun, Chen Xuan, Chen Wangsheng, Yang Qingqiang
Department of General Surgery (Gastrointestinal Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Front Genet. 2022 Mar 23;13:851373. doi: 10.3389/fgene.2022.851373. eCollection 2022.
Anti-cancer immunotherapeutic approaches have gained significant efficacy in multiple cancer types. However, not all patients with colorectal cancer (CRC) could benefit from immunotherapy due to tumor heterogeneity. The purpose of this study was to construct an immune-related signature for predicting the immune characteristics and prognosis of CRC. RNA-sequencing data and corresponding clinical information of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal (ImmPort). Then, we utilized univariate, lasso regression, and multivariate cox regression to identify prognostic IRGs and develop the immune-related signature. Subsequently, a nomogram was established based on the signature and other prognostic factors, and its predictive capacity was assessed by receiver operating characteristic (ROC) and decision curve analysis (DCA). Finally, associations between the signature and the immune characteristics of CRC were assessed. In total, 472 samples downloaded from TCGA were divided into the training cohort (236 samples) and internal validation cohort (236 samples), and the GEO cohort was downloaded as an external validation cohort (122 samples). A total of 476 differently expressed IRGs were identified, 17 of which were significantly correlated to the prognosis of CRC patients. Finally, 10 IRGs were filtered out to construct the risk score signature, and patients were divided into low- and high-risk groups according to the median of risk scores in the training cohort. The high-risk score was significantly correlated with unfavorable survival outcomes and aggressive clinicopathological characteristics in CRC patients, and the results were further confirmed in the internal validation cohort, entire TCGA cohort, and external validation cohort. Immune infiltration analysis revealed that patients in the low-risk group infiltrated with high tumor-infiltrating immune cell (TIIC) abundances compared to the high-risk group. Moreover, we also found that the immune checkpoint biomarkers were significantly overexpressed in the low-risk group. The prognostic signature established by IRGs showed a promising clinical value for predicting the prognosis and immune characteristics of human CRC, which contribute to individualized treatment decisions.
抗癌免疫治疗方法在多种癌症类型中已取得显著疗效。然而，由于肿瘤异质性，并非所有结直肠癌（CRC）患者都能从免疫治疗中获益。本研究的目的是构建一个免疫相关特征，用于预测CRC的免疫特征和预后。从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取CRC患者的RNA测序数据及相应临床信息，并从免疫数据库和分析门户（ImmPort）下载免疫相关基因（IRG）。然后，我们利用单变量、套索回归和多变量Cox回归来识别预后IRG并构建免疫相关特征。随后，基于该特征和其他预后因素建立了列线图，并通过受试者工作特征（ROC）和决策曲线分析（DCA）评估其预测能力。最后，评估该特征与CRC免疫特征之间的关联。总共从TCGA下载的472个样本被分为训练队列（236个样本）和内部验证队列（236个样本），并下载GEO队列作为外部验证队列（122个样本）。共鉴定出476个差异表达的IRG，其中17个与CRC患者的预后显著相关。最后，筛选出10个IRG构建风险评分特征，并根据训练队列中风险评分的中位数将患者分为低风险组和高风险组。高风险评分与CRC患者不良生存结局和侵袭性临床病理特征显著相关，结果在内部验证队列、整个TCGA队列和外部验证队列中得到进一步证实。免疫浸润分析显示，与高风险组相比，低风险组患者的肿瘤浸润免疫细胞（TIIC）丰度较高。此外，我们还发现免疫检查点生物标志物在低风险组中显著过表达。由IRG建立的预后特征在预测人类CRC的预后和免疫特征方面显示出有前景的临床价值，这有助于做出个体化治疗决策。
