Harbor-UCLA Medical Center, Department of Pathology, Torrance, CA 90502, United States.
Harbor-UCLA Medical Center, Department of Pathology, Torrance, CA 90502, United States.
Exp Mol Pathol. 2018 Aug;105(1):144-149. doi: 10.1016/j.yexmp.2018.07.005. Epub 2018 Jul 17.
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer related deaths worldwide. Among others, non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the two major risk factors as both of them may develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated. However, patients with NASH progress to HCC at a rate around 0.5% annually, while 3-10% ASH patients may progress to HCC annually. The present study is to demonstrate the molecular differences in oncogenesis pathway between NASH and ASH. By using immunofluorescence study and quantitating the fluorescence intensity morphometrically in liver biopsied specimens from NASH and ASH patients, the protein expression of candidate molecules within hepatocytes cytoplasm are studied, including two HCC-related molecules FAT10 and FOXO1, and one GPCR pathway related molecule ADRA2A. Compared with the control group patients, the expression levels of all the molecules were upregulated in the ASH group of patients (p < 0.001 in all molecules), while FAT10 and ADRA2A were upregulated, FOXO1 did not change in the NASH group of patients. The most important finding is that compared with the ASH group of patients, the expression levels of all three molecules were significantly lower than in the NASH group of patients (p < 0.001 in all molecules). These results confirmed our previous finding that there are significant differences of molecules change in ASH compared to NASH. Thus, we conclude that there are significantly different molecules and pathways involved during the pathogenesis of HCC development in ASH compared to NASH which could help explain why the tumorigenic rate is different in ASH and NASH.
肝细胞癌 (HCC) 是全球第五大常见癌症和第二大癌症相关死亡原因。非酒精性脂肪性肝炎 (NASH) 和酒精性脂肪性肝炎 (ASH) 是两个主要的风险因素，因为如果不治疗，两者都可能发展为肝硬化和肝细胞癌 (HCC)。然而，NASH 患者每年进展为 HCC 的速度约为 0.5%，而 3-10%的 ASH 患者每年可能进展为 HCC。本研究旨在展示 NASH 和 ASH 之间致癌途径的分子差异。通过使用免疫荧光研究并对 NASH 和 ASH 患者肝活检标本进行形态计量学定量荧光强度，研究了肝细胞细胞质中候选分子的蛋白表达，包括两个与 HCC 相关的分子 FAT10 和 FOXO1，以及一个 GPCR 途径相关的分子 ADRA2A。与对照组患者相比，所有分子在 ASH 组患者中的表达水平均上调（所有分子均 p < 0.001），而 FAT10 和 ADRA2A 上调，FOXO1 在 NASH 组患者中未发生变化。最重要的发现是，与 ASH 组患者相比，所有三种分子的表达水平均明显低于 NASH 组患者（所有分子均 p < 0.001）。这些结果证实了我们之前的发现，即 ASH 与 NASH 相比，分子变化存在显著差异。因此，我们得出结论，ASH 中 HCC 发展的发病机制涉及的分子和途径明显不同于 NASH，这可以帮助解释为什么 ASH 和 NASH 的致瘤率不同。
