Background

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Although the significant efficacy of immunotherapy has been shown, only limited CRC patients benefit from it. Therefore, we aimed to establish a prognostic signature based on immune-related genes (IRGs) to predict overall survival (OS) and the potential response to immunotherapy in CRC patients.

Methods

Gene expression profiles and clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The prognostic signature composed of IRGs was established using univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis. CIBERSORT was used to estimate the immune cell infiltration.

Results

A total of 24 survival-related IRGs were identified from 247 differentially expressed IRGs. Then, 16 IRGs were selected to establish the prognostic signature that stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The AUCs of the time-dependent ROC curves indicated that the signature had a strong predictive accuracy in internal and external validation sets. Multivariate cox regression analysis suggested that the signature could also act as an independent prognostic factor for OS. The low-risk group had a higher proportion of immune cell infiltration than the high-risk group, such as CD4 memory resting T cells, activated dendritic cells, and resting dendritic cells. In addition, patients in the high-risk group exhibited higher tumor mutation burden and BRAF mutation.

Conclusion

We developed an immune-related prognostic signature to predict the OS and immune status in CRC patients. We believed that our signature is conducive to better stratification and more precise immunotherapy for CRC patients.

中文翻译：

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大肠癌免疫预后标记的鉴定和验证。

背景

大肠癌（CRC）是世界上最常见的恶性肿瘤之一。尽管已经显示出免疫疗法的显着疗效，但只有有限的CRC患者可以从中受益。因此，我们旨在基于免疫相关基因（IRG）建立预后标记，以预测CRC患者的总体生存率（OS）和对免疫疗法的潜在反应。

方法

CRC患者的基因表达谱和临床信息来自癌症基因组图谱（TCGA）和基因表达综合（GEO）数据库。使用单变量Cox回归和最小绝对收缩和选择算子（LASSO）回归分析建立了由IRG组成的预后标志。CIBERSORT用于估计免疫细胞浸润。

结果

从247个差异表达的IRG中鉴定出总共24个与生存相关的IRG。然后，选择16个IRGs建立预后特征，将患者分为具有统计学差异的生存结果的高风险和低风险组。随时间变化的ROC曲线的AUC表示该签名在内部和外部验证集中具有很强的预测准确性。多变量Cox回归分析表明，签名也可以作为OS的独立预后因素。低风险组的免疫细胞浸润比例高于高风险组，例如CD4记忆静息T细胞，活化树突状细胞和静息树突状细胞。此外，高危组的患者表现出更高的肿瘤突变负担和BRAF突变。

结论

我们开发了一种与免疫有关的预后信号，以预测CRC患者的OS和免疫状态。我们认为，我们的签名有利于CRC患者更好的分层和更精确的免疫疗法。