Background

As a new method for predicting tumor prognosis, the predictive effect of immune-related gene pairs (IRGPs) has been confirmed in several cancers, but there is no comprehensive analysis of the clinical significance of IRGPs in gastric cancer (GC).

Method

Clinical and gene expression profile data of GC patients were obtained from the GEO database. Based on the ImmPort database, differentially expressed immune-related gene (DEIRG) events were determined by a comparison of GC samples and adjacent normal samples. Cox proportional regression was used to construct an IRGP signature, and its availability was validated using three external validation datasets. In addition, we explored the association between clinical data and immune features and established a nomogram to predict outcomes in GC patients.

Result

A total of 88 DEIRGs were identified in GC from the training set, which formed 3828 IRGPs. Fourteen overall survival (OS)-related IRGPs were used to construct the prognostic signature. As a result, patients in the high-risk group exhibited poorer OS compared to those in the low-risk group. In addition, the fraction of CD8+ T cells, plasma cells, CD4 memory activated T cells, and M1 macrophages was higher in the high-risk group. Expression of two immune checkpoints, CD276 and VTCN1, was significantly higher in the high-risk group as well. Based on the independent prognostic factors, a nomogram was established and showed excellent performance.

Conclusion

The 14 OS-related IRGP signature was associated with OS, immune cells, and immune checkpoints in GC patients, and it could provide the basis for related immunotherapy.

中文翻译：

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全面分析14个与免疫相关的基因对签名，以预测胃癌的预后和免疫特征

背景

作为预测肿瘤预后的一种新方法，已经在几种癌症中证实了免疫相关基因对（IRGPs）的预测作用，但尚未全面分析IRGPs在胃癌（GC）中的临床意义。

方法

从GEO数据库获得GC患者的临床和基因表达谱数据。根据ImmPort数据库，通过比较GC样品和相邻正常样品来确定差异表达的免疫相关基因（DEIRG）事件。使用Cox比例回归构建IRGP签名，并使用三个外部验证数据集验证了其可用性。此外，我们探索了临床数据与免疫功能之间的关联，并建立了诺模图以预测GC患者的预后。

结果

从训练集中的GC中总共鉴定出88个DEIRG，形成了3828个IRGP。使用十四个总体生存（OS）相关的IRGP来构建预后标志。结果，与低风险组相比，高风险组的患者的OS较差。此外，高风险组中CD8 + T细胞，浆细胞，CD4记忆激活的T细胞和M1巨噬细胞的比例更高。在高风险组中，两个免疫检查点CD276和VTCN1的表达也明显更高。基于独立的预后因素，建立了诺模图，并显示出优异的性能。

结论

14种与OS相关的IRGP签名与GC患者的OS，免疫细胞和免疫检查点相关，并且可以为相关免疫治疗提供基础。