RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:High Midkine Expression Correlates with Poor Prognosis and Immune Cell Infiltration in Hepatocellular Carcinoma.
High Midkine Expression Correlates with Poor Prognosis and Immune Cell Infiltration in Hepatocellular Carcinoma.
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HCC 中 MDK 高表达与患者不良结局相关,并影响免疫细胞浸润。
通过生物信息学分析和实验验证,研究中期因子(MDK)在肝细胞癌(HCC)中的作用,重点关注其与肿瘤免疫微环境及患者预后的关系。
利用GEPIA数据库分析MDK在不同癌症类型中的表达模式,特别比较HCC与正常组织。采用免疫组织化学(IHC)检测100对HCC及癌旁组织样本,验证MDK表达。通过Kaplan-Meier和Cox回归进行生存分析。利用TIMER 2.0数据库研究MDK表达与免疫细胞浸润的关系,并通过免疫细胞标志物IHC染色进行验证。
与癌旁正常组织相比,HCC组织MDK表达显著升高。MDK高表达与肿瘤数目、血管侵犯、临床分期较晚及预后不良密切相关,并是独立预后因素。值得注意的是,MDK高表达可预测接受免疫治疗患者结局较差。数据库和IHC分析显示,MDK表达与调节性T(Treg)细胞浸润呈正相关,与自然杀伤(NK)细胞浸润呈负相关,提示MDK可能参与塑造肿瘤免疫微环境。
HCC中MDK高表达与患者不良结局相关,并影响免疫细胞浸润。MDK可能成为HCC治疗的新型预后生物标志物和潜在治疗靶点。
This study investigated the role of MDK (Midkine) in hepatocellular carcinoma (HCC) through bioinformatics analysis and experimental validation, focusing on its relationship with tumor immune microenvironment and patient prognosis.
We employed the GEPIA database to analyze MDK expression patterns across cancer types and specifically in HCC versus normal tissues. MDK expression was validated through immunohistochemistry (IHC) in 100 paired HCC and adjacent tissue samples. Survival analyses were conducted using Kaplan-Meier and Cox regression methods. The relationship between MDK expression and immune cell infiltration was investigated using TIMER 2.0 database and verified through IHC staining of immune cell markers.
MDK expression was significantly elevated in HCC tissues compared to adjacent normal tissues. High MDK expression strongly correlated with tumor number, vascular invasion, advanced clinical stage and poor prognosis, serving as an independent prognostic factor. Notably, elevated MDK expression predicted poor outcomes in patients receiving immunotherapy. Database analysis and IHC analysis revealed that MDK expression positively correlated with regulatory T (Treg) cell infiltration while negatively correlating with natural killer (NK) cell presence, suggesting its role in shaping the tumor immune microenvironment.
High MDK expression in HCC correlates with unfavorable patient outcomes and impacts immune cell infiltration. MDK may serve as a novel prognostic biomarker and potential therapeutic target in HCC treatment.
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