Department of Pathology, Key Laboratory for Tumor Metastasis and Intervention of Liaoning Province, Dalian Medical University, Dalian Liaoning, China.
Biofactors. 2017 Sep 10;43(5):662-672. doi: 10.1002/biof.1368. Epub 2017 Jun 13.
Hepatocellular carcinoma (HCC) ranks in the top of cancers leading to death. Early diagnosis is the big challenge in the case of HCC. Our in vitro study showed that Ezrin expression in lymphatic metastasis hepatocellular carcinoma (LNM-HCC) was associated with the metastatic rate. Here we aim to evaluate Ezrin expression as diagnostic and/or prognostic biomarker of LNM-HCC in mice. Chinese inbred 615 mice, Hca-F and Hca-P cell lines were used in the study. Histological changes were determined by Hematoxylin and Eosin, while Ezrin expression was assessed by qRT-PCR, western blot, immunohistochemistry, and enzyme-linked immunosorbent assay. Ezrin expression in this study gives credit to our in vitro study which Ezrin expression was positively correlated with LNM-HCC and negatively with Annexin7 (A7) expression. The highest histological changes were observed in high metastatic primary/secondary tumors combined with high Ezrin expression. Ezrin and A7 are higher in total primary tumors than in total secondary tumors (P = 0.0001, P = 0.021), respectively. Ezrin expression was enhanced in Hca-P A7 down-regulated primary/secondary tumors (P = 0.004), whereas, Ezrin expression was suppressed in Hca-F A7 upregulated primary/secondary tumors. Serum ELISA indicated differential expression of Ezrin among the study groups (P ≤ 0.0001). Ezrin expression was higher in NC-Hca-F than NC-Hca-P (P ≤ 0.0001), suppressed in Hca-F A7 upregulation (P ≤ 0.0001) and in enhanced in Hca-P A7 down-regulation (P = 0.0001). In conclusion, Ezrin level may serve as a differential diagnostic and/or prognostic biomarker for high and low LNM-HCC and may be beneficial in the diagnosis of HCC disease. © 2017 BioFactors, 43(5):662-672, 2017.
肝细胞癌 (HCC) 在导致死亡的癌症中排名最高。早期诊断是 HCC 的一大挑战。我们的体外研究表明，淋巴转移肝癌 (LNM-HCC) 中的 Ezrin 表达与转移率有关。在这里，我们旨在评估 Ezrin 表达作为 LNM-HCC 的诊断和/或预后生物标志物在小鼠中的表达。本研究使用中国近交系 615 小鼠、Hca-F 和 Hca-P 细胞系。通过苏木精和伊红染色确定组织学变化，通过 qRT-PCR、western blot、免疫组织化学和酶联免疫吸附试验评估 Ezrin 表达。本研究中的 Ezrin 表达与我们的体外研究一致，Ezrin 表达与 LNM-HCC 呈正相关，与 Annexin7 (A7) 表达呈负相关。在高转移性原发/继发肿瘤中观察到最高的组织学变化，同时 Ezrin 表达也升高。Ezrin 和 A7 在总原发肿瘤中的表达均高于总继发肿瘤（P=0.0001，P=0.021）。在 Hca-P A7 下调的原发/继发肿瘤中 Ezrin 表达增强（P=0.004），而在 Hca-F A7 上调的原发/继发肿瘤中 Ezrin 表达受到抑制。血清 ELISA 表明 Ezrin 在研究组中的表达存在差异（P≤0.0001）。NC-Hca-F 中的 Ezrin 表达高于 NC-Hca-P（P≤0.0001），在 Hca-F A7 上调时受到抑制（P≤0.0001），在 Hca-P A7 下调时增强（P=0.0001）。总之，Ezrin 水平可作为 LNM-HCC 高低的差异诊断和/或预后生物标志物，有助于 HCC 疾病的诊断。
