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
CLGN 在肝细胞癌中的上调可能受 hsa-miR-194-3p 调控，并与患者进展相关
英文原题：The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression.
查看英文原题
The upregulation of CLGN in hepatocellular carcinoma is potentially regulated by hsa-miR-194-3p and associated with patient progression.
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研究概要
CLGN 在 HCC 中的上调与患者不良预后显著相关，尤其是在晚期阶段，并可能受 hsa-miR-194-3p 调控。这些发现提示 CLGN 可能与 HCC 进展密切相关，是晚期 HCC 患者潜在的治疗靶点和预后指标。
研究思路结论见上方概要
背景
肝细胞癌（HCC）患者预后较差，尤其是在晚期阶段。靶向治疗是晚期HCC患者的主要治疗手段，但HCC的最佳治疗靶点仍知之甚少。本研究的主要目的是识别潜在的新型预后标志物和治疗靶点。
方法
首先，从Gene Expression Omnibus (GEO)数据库中鉴定出HCC中的差异表达基因(DEGs)。利用GEPIA、TIMER、HPA、Kaplan Meier Plotter、CBioPortal、miRWalk、TargetScan和ENCORI数据库分析了DEGs的表达、预后意义及潜在机制。采用免疫组化染色法测定潜在候选基因的蛋白表达水平。
结果
MND1、STXBP6和CLGN的mRNA水平在HCC中显著升高（p < 0.01）。CLGN mRNA水平升高的HCC患者总生存期（OS）、无病生存期（DFS）、无进展生存期（PFS）和疾病特异性生存期（DSS）较差（p < 0.05）。较高的MND1 mRNA水平与HCC患者较差的DFS显著相关（p < 0.05）。然而，STXBP6表达与HCC预后之间无显著相关性（p > 0.05）。进一步分析显示，病理分期较晚且CLGN mRNA表达升高的患者预后较差（p < 0.01）。此外，与正常组织相比，HCC中CLGN蛋白水平升高。CLGN的mRNA水平与HCC中六种常见TIL（肿瘤浸润淋巴细胞）的丰度无显著相关性（COR < 0.5）。此外，CLGN在HCC患者中的突变率低于1%（10/1089）。最后，hsa-miR-194-3p在HCC中的表达水平显著低于正常组织（p < 0.05），且hsa-miR-194低表达的HCC预后较差（p < 0.05）。
展开英文摘要原文
BACKGROUND
Patients with hepatocellular carcinoma (HCC) have poor prognosis, especially in advanced stages. Targeted therapy is the main treatment for advanced HCC patients, but the optimal targets for HCC remain poorly understood. The main purpose of this study was to identify potential novel prognostic markers and therapeutic targets.
METHODS
Firstly, differentially expressed genes (DEGs) in HCC were identified from the Gene Expression Omnibus (GEO) database. The expression, significance in prognosis, and potential mechanisms of DEGs were analyzed using GEPIA, TIMER, HPA, Kaplan Meier Plotter, CBioPortal, miRWalk, TargetScan, and ENCORI databases. Immunohistochemical staining was used to determine the protein expression levels of potential candidate genes.
RESULTS
The mRNA levels of MND1 , STXBP6 , and CLGN were significantly increased in HCC ( p < 0.01). HCC patients with elevated CLGN mRNA levels had poorer overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS) ( p < 0.05). Higher MND1 mRNA levels significantly correlated with poorer DFS in HCC patients ( p < 0.05). However, there was no significant correlation between STXBP6 expression and prognosis of HCC ( p > 0.05). Further analysis revealed that patients with elevated CLGN mRNA expression in advanced pathology stages had poorer prognosis ( p < 0.01). In addition, CLGN protein levels were elevated in HCC compared to their levels in normal tissues. The mRNA levels of CLGN had no significant correlation with the abundance of six common tumor infiltrating lymphocytes in HCC (COR < 0.5). Moreover, the mutation rate of CLGN was less than 1% in HCC patients (10/1089). Finally, the expression level of hsa-miR-194-3p in HCC was significantly lower than that in normal tissues ( p < 0.05), and prognosis of HCC with low expression of hsa-miR-194 was poor ( p < 0.05).
CONCLUSION
The upregulation of CLGN in HCC is significantly associated with poor patient prognosis, especially in the advanced stages, and may be regulated by hsa-miR-194-3p. These findings suggest that CLGN may be closely related to the progression of HCC, and is a potential therapeutic target and prognostic indicator for patients with advanced HCC.
论文信息
- 作者
- Cui Z、Wang J、Chen G、Li D、Cheng B、Lai Y、Wu Z
- 单位
- Department of Hepatobiliary Disease, Dongfang Hospital, School of Medicine, Xiamen University, Fuzhou, China.China
- 期刊
- Frontiers in oncology2022
- 原文标识
- PubMed 36698420 · DOI 10.3389/fonc.2022.1081510
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