一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAV1 is a prognostic predictor for patients with idiopathic pulmonary fibrosis and lung cancer.
CAV1 is a prognostic predictor for patients with idiopathic pulmonary fibrosis and lung cancer.
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肺癌和特发性肺纤维化(IPF)的极高死亡率是一个全球性威胁。早期发现和诊断可以降低其死亡率。由于纤维化是癌症的必经过程,识别这两种疾病中涉及的共同潜在预后基因将显著有助于疾病预防和靶向治疗。从GEO数据库中提取了IPF和肺癌的微阵列数据集。利用GEO2R检索差异表达基因(DEGs)。通过Venn工具获得交集DEGs。使用DAVID工具对DEGs进行GO和KEGG通路富集分析。然后,采用Kaplan-Meier plotter确定预后价值,并在TCGA和GTEx数据库中验证枢纽基因的表达、病理分期和磷酸化水平。
最后,通过TIMER2工具评估肺癌中免疫细胞浸润的程度。Venn图揭示了来自肺癌GSE32863、GSE43458、GSE118370和GSE75037以及IPF GSE2052和GSE53845的1个上调基因和15个下调基因。CytoHubba根据连接度确定前三个基因[TEK受体酪氨酸激酶(TEK)、小窝蛋白1(CAV1)和内皮黏蛋白(EMCN)]为枢纽基因。生存分析表明只有TEK和CAV1的表达与总生存期(OS)和无进展生存期(FP)相关。病理分期分析揭示只有CAV1表达与病理分期相关,并且只有CAV1磷酸化表达水平与肺癌显著相关。
此外,在肺癌中,癌症相关成纤维细胞、内皮细胞和中性粒细胞的免疫浸润与CAV1表达之间观察到统计学上的正相关,而T细胞滤泡辅助细胞的免疫浸润则呈现出相反的结果。通过联合筛选IPF和肺癌中的关键基因,肺癌的早期检测和诊断潜力得到了改善。
The extremely high mortality of both lung cancer and Idiopathic pulmonary fibrosis (IPF) is a global threat. Early detection and diagnosis can reduce their mortality. Since fibrosis is a necessary process of cancer, identifying the common potential prognostic genes involved in these two diseases will significantly contribute to disease prevention and targeted therapy. Microarray datasets of IPF and lung cancer were extracted from the GEO database.
GEO2R was exploited to retrieve the differentially expressed genes (DEGs). The intersecting DEGs were obtained by the Venn tool. DAVID tools were used to perform GO and KEGG pathway enrichment analysis of DEGs. Then, the Kaplan-Meier plotter was employed to determine the prognostic value and verify the expression, pathological stage, and phosphorylation level of the hub gene in the TCGA and GTEx database.
Finally, the extent of immune cell infiltration in lung cancer was estimated by the TIMER2 tool. The Venn diagram revealed 1 upregulated gene and 15 downregulated genes from GSE32863, GSE43458, GSE118370, and GSE75037 of lung cancer, as well as GSE2052 and GSE53845 of IPF. CytoHubba identified the top three genes [TEK receptor tyrosine kinase (TEK), caveolin 1 (CAV1), and endomucin (EMCN)] as hub genes following the connectivity degree.
Survival analysis claimed the association of only TEK and CAV1 expression to both overall survival (OS) and first progression (FP). Pathological stage analyses revealed the relationship of only CAV1 expression to the pathological stage and the significant correlation of only CAV1 phosphorylation expression level for lung cancer.
Furthermore, a statistically positive correlation was observed between the immune infiltration of cancer-associated fibroblasts, endothelial, and neutrophils with the CAV1 expression in lung cancer, whereas the contradictory result was noted for the immune infiltration of T cell follicular helper. Early detection and diagnostic potential of lung cancer are ameliorated by the combined selection of key genes among IPF and lung cancer.
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