Background: Stomach adenocarcinoma (STAD) is one of the most prevalent malignances and ranks fifth in incidence and third in the cancer-related deaths among all malignances. The prognosis of STAD is poor. Immunotherapy based on immune checkpoint blockade is ever-increasingly suggested as the most promising therapy strategy for STAD. However, the prognosis and therapy value of immune checkpoints in STAD is far from clarified.
Methods: In our study, bioinformatics methods were performed to explore the expression and prognosis value of immune checkpoints in STAD and their association with immune infiltration. qRT-PCR was performed to verify our result.
Results: Most of the immune checkpoints were upregulated in STAD. There were lots of genetic mutations among immune checkpoints in STAD, including missense_mutation, frame_shift_del et al. Interestingly, most of immune checkpoints were associated with drug sensitivity and drug resistance. Moreover, CD274, PVR, LGALS9, ICOSLG and CD70 were associated with the overall survival, post progression survival and first progression in STAD. The univariate and multivariate analysis revealed that CD70, ICOSLG, age, pTNM stage, and radiation therapy were independent factors affecting the prognosis of STAD patients. The expression of ICOSLG and CD70 was correlated with immune cells as well as immune biomarkers, including CD8+ T cells, CD4+ T cells, macrophage, neutrophils and dendritic cells.
Conclusion: All in all, our study performed a comprehensive analysis of the prognostic value and immune function of immune checkpoints in STAD, and our result suggested that immune checkpoint ICOSLG and CD70 serve as prognostic biomarkers and associate with immune infiltration in STAD.



中文翻译：

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胃腺癌免疫检查点预后价值及免疫功能综合分析

背景：胃腺癌 (STAD) 是最常见的恶性肿瘤之一，在所有恶性肿瘤中发病率排名第五，癌症相关死亡人数排名第三。STAD的预后较差。基于免疫检查点阻断的免疫疗法越来越多地被认为是 STAD 最有希望的治疗策略。然而，免疫检查点在 STAD 中的预后和治疗价值远未阐明。
方法：本研究采用生物信息学方法探讨免疫检查点在STAD中的表达和预后价值及其与免疫浸润的关系。进行 qRT-PCR 以验证我们的结果。
结果：大多数免疫检查点在 STAD 中上调。STAD的免疫检查点存在大量基因突变，包括missense_mutation、frame_shift_del等。有趣的是，大多数免疫检查点与药物敏感性和耐药性有关。此外，CD274、PVR、LGALS9、ICOSLG 和 CD70 与 STAD 的总生存期、进展后生存期和首次进展相关。单因素和多因素分析显示CD70、ICOSLG、年龄、pTNM分期、放疗是影响STAD患者预后的独立因素。ICOSLG 和 CD70 的表达与免疫细胞以及免疫生物标志物相关，包括 CD8+ T 细胞、CD4+ T 细胞、巨噬细胞、中性粒细胞和树突状细胞。
结论：总而言之，我们的研究对 STAD 中免疫检查点的预后价值和免疫功能进行了综合分析，我们的结果表明免疫检查点 ICOSLG 和 CD70 作为 STAD 中的预后生物标志物并与免疫浸润相关。