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:High TLX1 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Lung Adenocarcinoma.
High TLX1 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Lung Adenocarcinoma.
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在 LUAD 患者中发现 TLX1 高表达与不良生存和免疫浸润之间存在关联。TLX1 在 LUAD 的诊断、预后和免疫治疗中可能具有潜在作用。
为制定肺腺癌(LUAD)的最佳个体化治疗,迫切需要与预后相关的潜在生物标志物。T细胞白血病同源盒1(TLX1)在LUAD中的作用尚不清楚。
本研究通过TCGA数据库分析、生物信息学分析和实验验证,探讨了TLX1与LUAD的关系。
我们检测了TLX1在泛癌和LUAD中的表达,TLX1表达与临床特征、免疫浸润的关系,其诊断和预后价值,以及TLX1相关通路。分析包括多种统计方法,包括Kaplan-Meier法、Cox回归分析、GSEA和免疫浸润分析。使用qRT-PCR验证了LUAD细胞系中TLX1的表达。
在LUAD患者中,TLX1高表达与T分期相关(P<0.001)。TLX1高表达与较差的总生存期(OS)相关(HR:1.57;95% CI:1.18-2.1;P=0.002)。并且TLX1(HR:1.619;95% CI:1.012-2.590;P=0.044)与LUAD患者的OS独立相关。TLX1表达与以下通路相关,包括Rho GTPase效应因子、DNA修复、响应WNT的TCF依赖性信号传导、核受体信号传导、Notch信号传导、染色质修饰酶、ESR介导的信号传导、细胞衰老以及Runx1的转录调控。TLX1表达与aDC、Tcm和TReg细胞相关。与BEAS-2B细胞相比,LUAD细胞中TLX1的表达显著升高。
To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD.
In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation.
We examined the expression of TLX1 in pan cancer and LUAD, the relationship between TLX1 expression and clinical features, immune infiltration, its diagnostic and prognostic value, as well as TLX1 related pathways. The analysis included various statistical methods, including the Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis. TLX1 expression in LUAD cell lines was validated using qRT-PCR. RESULT: In LUAD patients, high expression of TLX1 was associated with T stage (P<0.001). High TLX1 expression was associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.18-2.1; P=0.002). And TLX1 HR: 1.619; 95% CI: 1.012-2.590; P=0.044) was independently correlated with OS in LUAD patients. TLX1 expression was associated with the pathways, including Rho GTPase effectors, DNA repair, TCF dependent signaling in response to WNT, signaling by Nuclear Receptors, signaling by Notch, chromatin-modifying enzymes, ESR-mediated signaling, cellular senescence, and transcriptional regulation by Runx1. TLX1 expression was correlated with aDC, Tcm, and TReg cells. The expression of TLX1 was significantly increased in LUAD cells compared to BEAS-2B cells.
An association between high TLX1 expression and poor survival and immune infiltration was found in LUAD patients. There may be a potential role for TLX1 in diagnosis, prognosis, and immunotherapy for LUAD.
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