Li Juan, Zhao Ming, Fan Weiwei, Na Na, Chen Hui, Liang Ming, Tai Sheng, Yu Shan
Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.
Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Sichuan, PR China.
Histol Histopathol. 2025 Apr;40(4):523-540. doi: 10.14670/HH-18-794. Epub 2024 Jul 12.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In the present study, we evaluated SIRT4 expression levels in HCC specimens and investigated the relationships between SIRT4 expression levels, clinicopathological factors, and microvascular infiltration (MVI) in HCC.
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.
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 (=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 (=0.003), tumor size (<0.001), alpha fetoprotein (AFP) (=0.001), alanine aminotransferase (ALT) (=0.024), and γ-glutamyl transferase (γ-GT) (=0.024). However, SIRT4 was not an independent prognostic marker of HCC.
Our results demonstrated an association between SIRT4 expression levels, MVI, immune cell infiltration, and potential biological functions, including EMT in the progression of HCC.
肝细胞癌（HCC）是全球癌症死亡的第三大主要原因。在本研究中，我们评估了HCC标本中SIRT4的表达水平，并研究了SIRT4表达水平、临床病理因素与HCC微血管浸润（MVI）之间的关系。
通过免疫组织化学染色检测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证明SIRT4的生物学功能和表达相关的预后价值。
在所有相邻的非肿瘤性肝组织中均观察到SIRT4的弥漫性细胞质表达模式。HCC中SIRT4的水平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，HCC组织中SIRT4的表达水平显著降低（=0.003），但与总体临床结局无关。为了解释SIRT4对MVI的调节作用，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，并下调癌症相关成纤维细胞。此外，MVI与细胞分化程度（=0.003）、肿瘤大小（<0.001）、甲胎蛋白（AFP）（=0.001）、谷丙转氨酶（ALT）（=0.024）和γ-谷氨酰转移酶（γ-GT）（=0.024）之间存在显著关系。然而，SIRT4不是HCC的独立预后标志物。
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在HCC进展中存在关联。
