Department of Hepato-Biliary-Pancreatic Surgery, Navy General Hospital of Chinese People's Liberation Army, Beijing 100048, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing 100142, China.
World J Gastroenterol. 2018 Jul 7;24(25):2733-2740. doi: 10.3748/wjg.v24.i25.2733.
To understand the cellular and molecular changes in peripheral blood that can lead to the development of hepatocellular carcinoma (HCC) and provide new methods for its diagnosis and treatment.
Peripheral blood mononuclear cells were isolated from the peripheral blood of HCC patients and normal controls and then analyzed by flow cytometry. The percentage of transforming growth factor-β (TGF-β)+ regulatory cells (Tregs) in the peripheral blood was measured, and the expression of TGF-β was also determined. Then, the relationship between the changes and the 5-year survival of patients was analyzed. In addition, recombinant human TGF-β (rhTGF-β) and recombinant human interleukin-6 were added to stimulate the cultured cells, and their effects on HCC were evaluated.
The expression of TGF-β and the percentage of TGF-β+ Tregs in the peripheral blood of HCC patients increased significantly compared with normal controls. Compared with the low TGF-β expression group, the high TGF-β expression group had a significantly lower 5-year survival rate, and the same result was found in the two TGF-β+ Treg groups, suggesting that TGF-β and TGF-β+ Tregs were negatively correlated with the overall survival of the patients. In addition, rhTGF-β promoted the growth of tumor cells and induced high expression levels of IL-6, which further promoted tumor proliferation.
The results showed that TGF-β may promote tumor growth and proliferation by inducing the production of IL-6, and TGF-β and TGF-β+ Tregs may serve as new markers for predicting a poor prognosis in HCC.
了解外周血中导致肝细胞癌(HCC)发生的细胞和分子变化,为其诊断和治疗提供新方法。
分离 HCC 患者和正常对照者外周血中的单个核细胞,并用流式细胞术进行分析。测量外周血中转化生长因子-β(TGF-β)+调节性 T 细胞(Tregs)的百分比,并测定 TGF-β的表达量。然后,分析这些变化与患者 5 年生存率之间的关系。此外,添加重组人 TGF-β(rhTGF-β)和重组人白细胞介素-6(rhIL-6)刺激培养的细胞,评估它们对 HCC 的影响。
与正常对照组相比,HCC 患者外周血中 TGF-β的表达和 TGF-β+Tregs 的百分比显著增加。与低 TGF-β表达组相比,高 TGF-β表达组的 5 年生存率显著降低,两个 TGF-β+Treg 组也有相同的结果,表明 TGF-β和 TGF-β+Tregs 与患者的总体生存率呈负相关。此外,rhTGF-β促进肿瘤细胞的生长,并诱导 IL-6 的高表达,进而促进肿瘤增殖。
结果表明,TGF-β可能通过诱导 IL-6 的产生来促进肿瘤的生长和增殖,TGF-β和 TGF-β+Tregs 可能成为 HCC 预后不良的新标志物。