Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
Clin Res Hepatol Gastroenterol. 2022 Aug-Sep;46(7):101991. doi: 10.1016/j.clinre.2022.101991. Epub 2022 Jul 2.
Intrahepatic cholangiocarcinoma (ICC) can invade and metastasize. EIF5A2 is involved in the invasive metastatic process of several digestive malignancies. However, its role in ICC is yet to be elucidated.
Immunohistochemistry (IHC) and Western blot (WB) were used to detect the level of EIF5A2 in the tumor specimens of ICC patients and evaluate the correlation between its expression and clinicopathological characteristics. The significance of EIF5A2 in the prognosis of ICC patients was further evaluated by Kaplan-Meier and Cox regression analysis. In addition, CCK-8, EdU, Transwell invasion, and scratch assays were utilized to detect tumor cell proliferation, invasion, and metastasis. Furthermore, the role of EIF5A2 in ICC cells was evaluated after modification of EIF5A2 expression.
The level of EIF5A2 protein was significantly higher in ICC than in adjacent tissues. This high expression in the tumor samples was significantly associated with malignant phenotypes, such as lymph node metastasis (LNM), microvascular or bile duct invasion, and poor differentiation. ICC patients with high expression of EIF5A2 had short overall survival and a high cumulative recurrence rate. The multifactorial analysis showed that EIF5A2 is an independent prognostic marker. Furthermore, high levels of EIF5A2 may activate the PI3K/AKT/mTOR signaling pathway and upregulate Cyclin D1, Cyclin D3, MMP2, and MMP9 to promote ICC cell proliferation, migration, and invasion.
The current study found that EIF5A2 promotes ICC progression and is a prognostic biomarker and candidate therapeutic target for ICC patients.
肝内胆管癌（ICC）具有侵袭和转移的特性。EIF5A2 参与了几种消化道恶性肿瘤的侵袭转移过程。然而，其在 ICC 中的作用尚未阐明。
采用免疫组织化学（IHC）和 Western blot（WB）检测 ICC 患者肿瘤标本中 EIF5A2 的水平，并评估其表达与临床病理特征的相关性。通过 Kaplan-Meier 和 Cox 回归分析进一步评估 EIF5A2 对 ICC 患者预后的意义。此外，还利用 CCK-8、EdU、Transwell 侵袭和划痕实验检测肿瘤细胞的增殖、侵袭和转移。进一步通过修饰 EIF5A2 的表达来评估 EIF5A2 在 ICC 细胞中的作用。
EIF5A2 蛋白水平在 ICC 中明显高于相邻组织。肿瘤样本中 EIF5A2 的高表达与恶性表型显著相关，如淋巴结转移（LNM）、微血管或胆管侵犯和低分化。EIF5A2 高表达的 ICC 患者总生存率低，累积复发率高。多因素分析表明，EIF5A2 是独立的预后标志物。此外，EIF5A2 水平升高可能激活 PI3K/AKT/mTOR 信号通路，上调 Cyclin D1、Cyclin D3、MMP2 和 MMP9，从而促进 ICC 细胞的增殖、迁移和侵袭。
本研究发现 EIF5A2 促进 ICC 的进展，是 ICC 患者的预后生物标志物和潜在治疗靶点。
