研究动态
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死亡相关蛋白激酶 1 可预测各种癌症的预后和免疫治疗反应。

Death associated protein kinase 1 predicts the prognosis and the immunotherapy response of various cancers.

发表日期:2024 May 24
作者: Jianjian Yang, Ying Liu, Qing Geng, Bo Wang
来源: Cell Death & Disease

摘要:

死亡相关蛋白激酶 1 (DAPK1) 是一种钙/钙调蛋白依赖性丝氨酸/苏氨酸激酶,据报道它是一种肿瘤抑制因子,在多种组织中表达不平衡。但其在肿瘤免疫治疗中的功能尚不清楚。TCGA结果采用在线GEPIA2数据库支持。我们使用 cBioPortal 网络工具探索了 DAPK1 泛癌基因组改变分析。采用人类蛋白质图谱(HPA)来挖掘 DAPK1 蛋白质信息。我们使用 RT-qPCR 验证了肺腺癌样本中 DAPK1 的表达。随后分析DAPK1的表达与临床分期的关系。我们使用TIMER2.0作为研究DAPK1相关免疫细胞浸润的主要平台。使用 Spearman 相关分析来分析 DAPK1 和免疫治疗生物标志物之间的关联。还检查了 TMB 和 MSI 表达。最后,我们使用Kaplan-Meier图来评估DAPK1表达与免疫治疗疗效之间的关系。DAPK1在大多数癌症类型中异常表达,并且在多种癌症中具有预后能力。基因突变是泛癌中最常见的 DAPK1 改变。 DAPK1蛋白主要定位于肿瘤细胞中心体。 DAPK1 还与免疫激活标志、免疫细胞浸润和免疫调节剂的表达显着相关。值得注意的是,DAPK1 还可以显着预测癌症患者对抗 PD1 和抗 CTLA-4 治疗的反应。我们的研究结果表明,DAPK1 不仅可能是癌症患者的有效预后因素,而且还可能作为一种有前景的预测性免疫治疗生物标志物。使用免疫检查点抑制剂治疗的癌症患者。© 2024。作者获得 Springer Nature B.V. 的独家许可。
Death Associated Protein Kinase 1 (DAPK1) is a calcium/calmodulin-dependent serine/threonine kinase, which has been reported to be a tumor suppressor with unbalanced expression in various tissues. However, its function in tumor immunotherapy is still unclear.The online GEPIA2 database was used to support TCGA results. We explored the DAPK1 pan-cancer genomic alteration analysis using the cBioPortal web tool. The Human Protein Atlas (HPA) was employed to mine DAPK1 protein information. We verified the expression of DAPK1 in lung adenocarcinoma samples using RT-qPCR. Subsequently, the relationship between the expression of DAPK1 and the clinical stage was analyzed. We used TIMER2.0 as the primary platform for studying DAPK1-related immune cell infiltration. Associations between DAPK1 and immunotherapy biomarkers were analyzed using Spearman correlation analysis. TMB and MSI expression was also examined. Finally, we used Kaplan-Meier Plots to evaluate the relationship between DAPK1 expression and the efficacy of immunotherapy.DAPK1 is aberrantly expressed in most cancer types and has prognostic power in various cancers. Gene mutation was the most common DAPK1 alteration across pan-cancers. The DAPK1 protein was mainly localized to tumor cell centrosomes. DAPK1 was also significantly associated with immune-activated hallmarks, immune cell infiltration, and the expression of immunomodulators. Notably, DAPK1 can also significantly predict responses to anti-PD1 and anti-CTLA-4 therapy in cancer patients.Our findings suggest that DAPK1 may not only be an effective prognostic factor in cancer patients but may also function as a promising predictive immunotherapy biomarker for cancer patients treated with immune checkpoint inhibitors.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.