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
SIRT4 与肝细胞癌的微血管浸润、免疫细胞浸润及上皮间质转化相关
英文原题：SIRT4 is associated with microvascular infiltration, immune cell infiltration, and epithelial mesenchymal transition in hepatocellular carcinoma.
查看英文原题
SIRT4 is associated with microvascular infiltration, immune cell infiltration, and epithelial mesenchymal transition in hepatocellular carcinoma.
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研究概要
我们的结果表明，SIRT4 表达水平、MVI、免疫细胞浸润以及包括 EMT 在内的潜在生物学功能与 HCC 进展相关。
研究思路结论见上方概要
目的
肝细胞癌（HCC）是全球第三大癌症死亡原因。在本研究中，我们评估了HCC标本中SIRT4的表达水平，并探讨了SIRT4表达水平、临床病理因素与HCC微血管侵犯（MVI）之间的关系。
方法
采用免疫组化染色检测108例HCC标本中SIRT4的表达水平。HCC标本中的MVI分为三种亚型：M0、M1和M2。进行综合生物信息学分析，以阐明SIRT4的生物学功能及与表达相关的预后价值。
结果
在所有癌旁非肿瘤肝组织中均观察到SIRT4的弥漫性细胞质表达模式。SIRT4的水平在HCC中高于任何其他类型的癌症和正常组织。此外，当MVI为M1或M2时，SIRT4在HCC组织中的表达水平显著降低（p=0.003），但与总体临床结局无关。为了解释SIRT4对MVI的调控，我们还发现SIRT4表达与上皮-间质转化（EMT）标志物、CD4+ T/NK细胞相关，并与癌症相关成纤维细胞下调相关。此外，MVI与细胞分化程度（p=0.003）、肿瘤大小（p<0.001）、甲胎蛋白（AFP）（p=0.001）、丙氨酸氨基转移酶（ALT）（p=0.024）和γ-谷氨酰转移酶（γ-GT）（p=0.024）之间存在显著关系。然而，SIRT4并非HCC的独立预后标志物。
展开英文摘要原文
METHODS
The expression levels of SIRT4 in 108 HCC specimens were examined by immunohistochemical staining. MVI in HCC specimens was divided into three subtypes: M0, M1, and M2. Comprehensive bioinformatics analysis was carried out to demonstrate SIRT4's biological functions and expression-related prognostic value.
RESULTS
The diffuse cytoplasmic expression pattern of SIRT4 was observed in all adjacent nonneoplastic liver tissues. The levels of SIRT4 were higher in HCC than in any other type of cancer and normal tissues. In addition, the expression levels of SIRT4 were significantly decreased in HCC tissues when MVI was M1 or M2 ( p =0.003) but were not related to the overall clinical outcome. To explain MVI regulated by SIRT4, we also found that SIRT4 expression correlated with epithelial-mesenchymal transition (EMT) markers and CD4+ T/NK cells and downregulated cancer-associated fibroblast cells. Also, there was a significant relationship between MVI and degree of cell differentiation ( p =0.003), tumor size ( p <0.001), alpha fetoprotein (AFP) ( p =0.001), alanine aminotransferase (ALT) ( p =0.024), and γ-glutamyl transferase (γ-GT) ( p =0.024). However, SIRT4 was not an independent prognostic marker of HCC.
CONCLUSIONS
Our results demonstrated an association between SIRT4 expression levels, MVI, immune cell infiltration, and potential biological functions, including EMT in the progression of HCC.
论文信息
- 作者
- Li J、Zhao M、Fan W、Na N、Chen H、Liang M、Tai S、Yu S
- 第一作者单位
- Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.China
- 通讯作者单位
- Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China. yushan@hrbmu.edu.cn.China
- 期刊
- Histology and histopathology2025 Apr
- 原文标识
- PubMed 39082202 · DOI 10.14670/HH-18-794