Genomic Analysis Uncovers the Prognostic and Immunogenetic Feature of Pyroptosis in Gastric Carcinoma: Indication for Immunotherapy.
Genomic Analysis Uncovers the Prognostic and Immunogenetic Feature of Pyroptosis in Gastric Carcinoma: Indication for Immunotherapy.
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基因组分析揭示胃癌焦亡的预后和免疫遗传学特征：免疫治疗的适应症
DOI：
10.3389/fcell.2022.906759
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发表时间：
2022
影响因子：
5.5
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中科院分区：
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癌症中上睑下垂与肿瘤免疫微环境(TIME)之间的关系尚不清楚。在此，我们旨在探讨胃下垂在胃癌中的作用及其与时间的关系。使用非监督聚类来识别与上睑下垂相关的簇。采用套索Cox回归方法建立上睑下垂危险评分。对临床病理和遗传资料进行分析，并对其风险评分进行分析。此外，还研究了在预测免疫治疗反应和筛选潜在的抗肿瘤药物方面，上睑下垂风险评分的可重复性。构建了三个预后不同、免疫细胞组成和特征不同的上睑下垂集群。低下垂风险评分的特征是活化的T细胞亚群和M1巨噬细胞增加，M2巨噬细胞减少，MSI状态和TMB增加。同时，低积分与PD-L1表达、抗原提呈标志物和干扰素-γ签名显著相关。在TCGA、3个外部公共验证和1个真实世界验证(SYSUCC)队列中，PR的5年AUC分别为0.67、0.62、0.65、0.67和0.67。多变量分析进一步验证了上睑下垂风险评分系统的预后表现，在五个队列中，R值分别为2.43、1.83、1.78、2.35和2.67(均为P<；0.05)。GSEA显示低积分组的DNA损伤修复通路显著丰富。最后，恶性下垂风险评分系统被证明在预测免疫治疗的反应和筛选潜在的抗肿瘤药物方面是有用的。我们的研究强调了胃下垂与时间的相互作用在胃癌中的关键作用。上睑下垂风险评分系统可以独立用于预测个体的存活率和对免疫治疗的反应。
Crosstalk between pyroptosis and tumor immune microenvironment (TIME) in cancer has yet to be elucidated. Herein, we aimed to explore the role of pyroptosis and its association with TIME in gastric cancer. Unsupervised clustering was performed to identify the pyroptosis-related clusters. Pyroptosis risk score was constructed using LASSO Cox regression. Clinicopathological and genetic data of pyroptosis clusters and pyroptosis risk scores were explored. Reproducibility of pyroptosis risk score in predicting response to immunotherapy and screening potential antitumor drugs was also investigated. Three pyroptosis clusters with distinct prognosis, immune cell fractions and signatures, were constructed. A low-pyroptosis risk score was characterized by increased activated T-cell subtype and M1 macrophage, decreased M2 macrophage, higher MSI status, and TMB. Meanwhile, low-score significantly correlated with PD-L1 expression, antigen presentation markers, and IFN-γ signature. The 5-year AUCs of PRS were 0.67, 0.62, 0.65, 0.67, and 0.67 in the TCGA, three external public and one real-world validation (SYSUCC) cohorts. Multivariable analyses further validated the prognostic performance of the pyroptosis risk scoring system, with HRs of 2.43, 1.83, 1.78, 2.35, and 2.67 (all p < 0.05) in the five cohorts. GSEA indicated significant enrichment of DNA damage repair pathways in the low-score group. Finally, the pyroptosis risk scoring system was demonstrated to be useful in predicting response to immunotherapy, and in screening potential antitumor drugs. Our study highlights the crucial role of interaction between pyroptosis and TIME in gastric cancer. The pyroptosis risk scoring system can be used independently to predict the survival of individuals and their response to immunotherapy.