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:Characterization of the function and clinical value of ERCC family genes in lung adenocarcinoma.
Characterization of the function and clinical value of ERCC family genes in lung adenocarcinoma.
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我们的研究揭示了 ERCC 家族成员在 LUAD 中多方面的生物学和临床意义。这些发现为 ERCC 家族基因在 LUAD 中的功能及其潜在的临床应用提供了新的见解。
ERCC基因负责编码参与碱基切除修复的酶,已被认为与多种癌症相关,并导致化疗耐药。然而,该基因家族在肺腺癌(LUAD)中的预后和治疗意义尚缺乏全面分析。
本研究通过生物信息学方法对LUAD中ERCC家族基因进行了多维评估,包括mRNA表达水平、基因甲基化和拷贝数变异(CNV),以及它们与临床结局、基因集变异和TIL(肿瘤浸润淋巴细胞)(TILs)的相关性。此外,我们在细胞系中评估了ERCC8的抗肿瘤作用,在实验水平上展示了其临床潜力。
总体而言,ERCC基因的表达与良好预后呈负相关,其中ERCC6L和ERCC8展现出最可靠的预测性能。ERCC基因的甲基化水平和CNV增加通常分别与其表达水平呈负相关和正相关。此外,GSVA分析提示ERCC表达与细胞周期和凋亡通路呈正相关,但与TSC/mTOR通路呈负相关。进一步而言,ERCC基因的表达与TILs及抗肿瘤药物反应呈现出复杂的关系。体外细胞实验结果表明,抑制ERCC8可减轻LUAD细胞的恶性表型。
This study conducted a multidimensional assessment of ERCC family genes in LUAD using bioinformatic approaches, including mRNA expression level, gene methylation, and copy number variation (CNV), as well as their correlations with clinical outcome, gene set variations, and tumor-infiltrating lymphocytes (TILs). In addition, We evaluated the anti-tumor effects of ERCC8 in cell lines, demonstrating its clinical potential on an experimental level.
Overall, the expression of ERCC genes exhibited a negative correlation with good prognosis, with ERCC6L and ERCC8 demonstrating the most reliable predictive performance. Gene methylation level and CNV increases of ERCC genes generally displayed negative and positive associations with their expression levels, respectively. Additionally, GSVA analysis suggested that ERCC expression was positively correlated with cell cycle and apoptosis pathways but negatively correlated to the TSC/mTOR pathway. Furthermore, the expression of ERCC genes exhibited a complex relationship with TILs and the response to anti-tumor drugs. The results of in vitro cellular experiments show that inhibiting ERCC8 can alleviate the malignant phenotype of LUAD cells. DISCUSSION: Our study revealed the multifaceted biological and clinical significance of ERCC family members in LUAD. These findings provide new insights into the function of ERCC family genes in LUAD and their potential clinical applications.
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