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携带 STK11 突变的肺腺癌患者接受免疫治疗后免疫细胞浸润减少,预后更差。

Less immune cell infiltration and worse prognosis after immunotherapy for patients with lung adenocarcinoma who harbored STK11 mutation.

机构信息

Department of Internal Medicine Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong University, Jinan, Shandong, China.

出版信息

Int Immunopharmacol. 2020 Jul;84:106574. doi: 10.1016/j.intimp.2020.106574. Epub 2020 May 12.

Abstract

The STK11 mutation defined a special subtype for patients with lung adenocarcinoma. The cBioPortal data platform was applied to analyze STK11 mutation frequency and the relationship between STK11 mutation and immune prognostic markers. The TIMER database was used to analyze the relationship between STK11 mutation and immune cell infiltration. The survival difference for lung adenocarcinoma patients harbored STK11 mutation who received immunotherapy also used the cBioPortal database. The results showed that STK11 mutation co-occurrence more KRAS and KEAP1 mutation and fewer TP53 and EGFR mutation (all, P < 0.05); the patients harbored STK11 mutation had a lower expression of PDL1 (P = 0.002), higher TMB score (P = 0.002), higher proportion of males and smoking history; the patients harbored STK11 mutation had fewer immune cell infiltration including B cell (P < 0.01), CD8+ T cell (P < 0.001), CD4+ T cell (P < 0.001), Macrophage (P < 0.001), Neutrophil (P < 0.001) and Dendritic cell (P < 0.001). Importantly, we found the patients harbored STK11 mutation who received immune checkpoint inhibitors have worse overall survival (OS) with median survival only 6 months. In conclusion, our study demonstrated that STK11 mutation defined a special subtype for lung adenocarcinoma patients with different co-occurrence gene mutation, lower PDL1 expression, fewer immune cell infiltration and worse OS benefit from immune checkpoint inhibitors.

摘要

STK11 突变定义了肺腺癌患者的一个特殊亚型。应用 cBioPortal 数据平台分析 STK11 突变频率及其与免疫预后标志物的关系。利用 TIMER 数据库分析 STK11 突变与免疫细胞浸润的关系。cBioPortal 数据库用于分析携带 STK11 突变的肺腺癌患者接受免疫治疗的生存差异。结果表明,STK11 突变与 KRAS 和 KEAP1 突变的共发生频率更高,而与 TP53 和 EGFR 突变的共发生频率更低(均 P<0.05);携带 STK11 突变的患者 PDL1 表达较低(P=0.002),TMB 评分较高(P=0.002),男性和吸烟史比例较高;携带 STK11 突变的患者免疫细胞浸润较少,包括 B 细胞(P<0.01)、CD8+T 细胞(P<0.001)、CD4+T 细胞(P<0.001)、巨噬细胞(P<0.001)、中性粒细胞(P<0.001)和树突状细胞(P<0.001)。重要的是,我们发现携带 STK11 突变的患者接受免疫检查点抑制剂治疗的总生存期(OS)更差,中位生存期仅为 6 个月。总之,我们的研究表明,STK11 突变定义了肺腺癌患者的一个特殊亚型,其具有不同的共发生基因突变、较低的 PDL1 表达、较少的免疫细胞浸润和较差的免疫检查点抑制剂治疗生存获益。

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