为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Hydroxysteroid 17-Beta Dehydrogenase 6 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.
Hydroxysteroid 17-Beta Dehydrogenase 6 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.
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HSD17B6 是一种潜在的预后生物标志物,可决定 HCC 的癌症进展,并与肿瘤免疫细胞浸润相关。
肝细胞癌(HCC)是全球常见的恶性肿瘤,预后较差。因此,寻找有价值的HCC预后生物标志物具有重要意义。本研究旨在识别HCC的新型预后生物标志物,并评估核心基因在HCC中的潜在作用。
采用加权基因共表达网络分析和蛋白质-蛋白质相互作用分析来识别重要的潜在预后基因。通过GEPIA、Oncomine、UALCAN和HPA数据库确认了枢纽基因的表达。此外,利用Kaplan-Meier plotter数据库对枢纽基因进行了生存分析。最后,我们通过GSEA、TIMER和TISIDB数据库研究了HCC中枢纽基因与免疫因素之间的关联。
HSD17B6在HCC中的表达显著低于正常组织。HSD17B6低表达与HCC患者较差的总生存期和无进展生存期相关,尤其是在疾病中期(II期和III期或III级)。HSD17B6与肿瘤浸润性B细胞、CD4+和CD8+T细胞、巨噬细胞、中性粒细胞和树突状细胞显示出强相关性。体细胞拷贝数改变可能是HSD17B6表达与免疫浸润负相关的主要原因。HCC中HSD17B6表达与多种免疫细胞标志物的表达呈负相关,包括耗竭T细胞标志物PD-1和CTLA-4,提示其在调节肿瘤免疫中的作用。
Hepatocellular carcinoma (HCC) is a common malignancy worldwide with poor outcomes. Therefore, it is important to identify a valuable prognostic biomarker for HCC. The present study aimed to identify novel prognostic biomarkers for HCC and evaluate the potential role of hub genes in HCC.
Weighted gene co-expression network analysis and protein-protein interaction analysis were performed to identify important potential prognostic genes. The expression of hub genes was confirmed by the GEPIA, Oncomine, UALCAN, and HPA database. Furthermore, survival analysis of hub genes was performed using the Kaplan-Meier plotter database. Finally, we investigated the association between hub genes and immune factors in HCC through GSEA, the TIMER, and TISIDB database.
HSD17B6 expression was significantly lower in HCC than in normal tissues. Low HSD17B6 expression is associated with poorer overall survival and progression-free survival in HCC patients, particularly at medium disease stages (stage II and III or grade III). HSD17B6 showed a strong correlation with tumor-infiltrating B cells, CD4 + and CD8 + T cells, macrophages, neutrophils, and dendritic cells. Somatic copy number alteration might be the main cause of the negative correlation between HSD17B6 expression and immune infiltration. HSD17B6 expression in HCC negatively correlated with the expression of several immune cell markers, including exhausted T cell markers, PD-1 and CTLA-4, suggesting its role in regulating tumor immunity.
HSD17B6 is a potential prognostic biomarker that determines cancer progression and is correlated with tumor immune cells infiltration in HCC.
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