Yeh Chun-Nan, Wu Ren-Chin, Cheng Chi-Tung, Tsai Chun-Yi, Chang Yau-Ren, Yeh Ta-Sen, Wu Tsung-Han, Lee Wei-Chen, Chiang Kun-Chun
Department of Surgery, Liver Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan,
Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan.
Cancer Manag Res. 2018 Nov 21;10:6049-6059. doi: 10.2147/CMAR.S186931. eCollection 2018.
More than 500,000 people suffered from hepatocelluar carcinoma (HCC) annually and the relative incidence to mortality rate indicates its unfavorable prognosis. Several studies have proved that heme-oxygenase-1 (HO-1) is indirectly engaged in the invasion and the metastasis of some types of malignancies, including breast cancer, prostate cancer, and lung cancer. The role of HO-1 in hepatitis B virus (HBV)-related HCC is still not clarified.
The Western blot, doubling time, cell cycle analysis, migration assay, invasion assay, gene transfection, xenograft animal model, immunohistochemistry staining, and clinical validation study were applied in this study.
HO-1 overexpression not only decreased the growth but also inhibited the migration and invasion in human HBV-HCC cells (Hep-3B vs PLC/PRF/5). The inhibitory effect on growth, migration, and invasion is further demonstrated by the overexpression of HO-1 in Hep-3B cell by transfection study. Furthermore, HO-1 decreasing the growth of HBV-HCC was confirmed in animal study. The clinical validation illustrated that higher HO1 expression was also associated with favorable disease-free survival of HBV-HCC patients who underwent hepatectomy.
We identified HO-1 as a favorable prognostic factor for HBV-HCC patients who underwent hepatectomy.
每年有超过50万人罹患肝细胞癌（HCC），其相对发病率与死亡率表明预后不佳。多项研究已证实，血红素加氧酶-1（HO-1）间接参与某些类型恶性肿瘤的侵袭和转移，包括乳腺癌、前列腺癌和肺癌。HO-1在乙型肝炎病毒（HBV）相关HCC中的作用仍未阐明。
本研究采用蛋白质免疫印迹法、倍增时间、细胞周期分析、迁移实验、侵袭实验、基因转染、异种移植动物模型、免疫组织化学染色及临床验证研究。
HO-1过表达不仅降低了人HBV-HCC细胞（Hep-3B与PLC/PRF/5）的生长，还抑制了其迁移和侵袭。转染研究通过在Hep-3B细胞中过表达HO-1进一步证明了其对生长、迁移和侵袭的抑制作用。此外，动物研究证实HO-1降低了HBV-HCC的生长。临床验证表明，较高的HO-1表达也与接受肝切除术的HBV-HCC患者的无病生存期良好相关。
我们确定HO-1是接受肝切除术的HBV-HCC患者的一个良好预后因素。
