Department of Infectious Diseases, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China.
Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated To Shandong University, 324#, Jing 5 Road, Jinan, 250021, China.
Int J Clin Oncol. 2020 Jul;25(7):1334-1345. doi: 10.1007/s10147-020-01675-0. Epub 2020 Apr 28.
Epithelium-specific ETS 3 (ESE3) is down-regulated frequently in several malignancies and involved in carcinogenesis and progression. However, ESE3 expression pattern and its relationship with clinical features and prognosis in hepatocellular carcinoma (HCC) are still largely unknown.
ESE3 expression was analyzed by quantitative real-time PCR and western blotting in HCC cell lines, and then, it was analyzed by immunohistochemistry in HCC tissues and peritumoral normal tissues from total 94 HCC patients. The relationship between ESE3 expression and clinical features was investigated to illustrate the potential prognostic value in HCC. ESE3 roles on HCC progression were evaluated in vitro and vivo by MTT assay and mice tumor model, respectively.
ESE3, mainly located in the cytoplasm, was remarkably down-regulated in HCC tissues and cell lines. Low ESE3 expression was positively associated with tumor progression and metastasis features. Kaplan-Meier analysis demonstrated that low ESE3 expression contributed to poor recurrence-free survival (RFS) and overall survival (OS) (both p < 0.01) of patients, and maintained its prognostic value in predicting poor RFS and OS of "Early-stage" HCC patients regardless of clinical features being studied. Multivariate survival analysis was also identified ESE3 as an independent prognostic factor for RFS (p = 0.05 for marginal significance) and OS (p = 0.031). ESE3 expression restoration in cells led to a significant inhibition in HepG2 cell proliferation in vitro and vivo (both p < 0.001).
Down-regulated ESE3 expression in HCC tissues could serve as a potential therapeutic target against HCC and appears to be as a poor prognostic indicator for prognosis, especially in "Early-stage" HCC patients.
上皮细胞特异性 ETS 3（ESE3）在多种恶性肿瘤中经常下调，参与致癌作用和进展。然而，ESE3 的表达模式及其与肝细胞癌（HCC）临床特征和预后的关系在很大程度上仍不清楚。
通过定量实时 PCR 和 Western blot 分析 HCC 细胞系中的 ESE3 表达，然后通过免疫组织化学分析 94 例 HCC 患者的 HCC 组织和肿瘤旁正常组织中的 ESE3 表达。研究 ESE3 表达与临床特征之间的关系，以说明其在 HCC 中的潜在预后价值。通过 MTT 测定和小鼠肿瘤模型分别在体外和体内评估 ESE3 对 HCC 进展的作用。
ESE3 主要位于细胞质中，在 HCC 组织和细胞系中明显下调。低 ESE3 表达与肿瘤进展和转移特征呈正相关。Kaplan-Meier 分析表明，低 ESE3 表达与患者无复发生存率（RFS）和总生存率（OS）不良有关（均 p<0.01），并且在无论研究的临床特征如何，都能保持对“早期”HCC 患者不良 RFS 和 OS 的预后价值。多变量生存分析也确定 ESE3 是 RFS（p=0.05，边缘显著）和 OS（p=0.031）的独立预后因素。细胞中 ESE3 表达的恢复导致 HepG2 细胞在体外和体内的增殖明显受到抑制（均 p<0.001）。
HCC 组织中下调的 ESE3 表达可作为针对 HCC 的潜在治疗靶点，并且似乎是预后不良的指标，尤其是在“早期”HCC 患者中。
