Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China.
Zhengzhou University Library, Zhengzhou University, Zhengzhou 450001, Henan, China.
Aging (Albany NY). 2020 Dec 19;12(24):26095-26120. doi: 10.18632/aging.202317.
The heterogeneity and complexity of tumor-immune microenvironments lead to diverse immunotherapy effects among colon cancer patients. It is crucial to identify immune microenvironment-related biomarkers and construct prognostic risk models. In this study, the immune and stromal scores of 415 cases from TCGA were calculated using the ESTIMATE algorithm. AXIN2, CCL22, CLEC10A, CRIP2, RUNX3, and TRPM5 were screened and established a prognostic immune-related gene (IRG) signature using by univariate, LASSO, and multivariate Cox regression models. The predicted performance of IRG signature was external validated by GSE39582 (n=519). Stratified survival analysis showed IRG signature was an effective predictor of survival in patients with different clinical characteristics. The protein expression level of six genes was validated by immunohistochemistry analysis. Difference analysis indicated the mutation rate, immune cell of resting NK cells and regulatory T cells infiltration and four immune checkpoints of PD-1, PD-L1, LAG3 and VSIR expression levels in the high-risk group were significantly higher than those in the low-risk group. A nomogram incorporating the gene signatures and clinical factors was demonstrated had a good accuracy (1-, 3-, and 5-year AUC= 0.799, 0.791, 0.738). Our study identified a novel IRG signature, which may provide some references for the clinical precision immunotherapy of patients.
肿瘤免疫微环境的异质性和复杂性导致结肠癌患者的免疫治疗效果各异。确定免疫微环境相关的生物标志物并构建预后风险模型至关重要。在这项研究中，使用 ESTIMATE 算法计算了来自 TCGA 的 415 例患者的免疫和基质评分。通过单变量、LASSO 和多变量 Cox 回归模型筛选并建立了 AXIN2、CCL22、CLEC10A、CRIP2、RUNX3 和 TRPM5 预后免疫相关基因 (IRG) 特征。IRG 特征的预测性能通过 GSE39582(n=519)进行了外部验证。分层生存分析表明，IRG 特征是不同临床特征患者生存的有效预测因子。通过免疫组织化学分析验证了六个基因的蛋白表达水平。差异分析表明，高危组的突变率、静止 NK 细胞和调节性 T 细胞浸润的免疫细胞以及四个免疫检查点 PD-1、PD-L1、LAG3 和 VSIR 的表达水平明显高于低危组。纳入基因特征和临床因素的列线图显示具有良好的准确性(1、3 和 5 年 AUC=0.799、0.791 和 0.738)。我们的研究确定了一个新的 IRG 特征，它可能为患者的临床精准免疫治疗提供一些参考。
