Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan.
Ann Surg Oncol. 2009 Nov;16(11):3176-82. doi: 10.1245/s10434-009-0614-2. Epub 2009 Jul 21.
As a pleiotropic cytokine, transforming growth factor-beta (TGF-beta) controls the functions of proliferation, adhesion, and differentiation, and contributes to cancer promotion and suppression. Moreover, it is related to the epithelial-mesenchymal transition process and T cell differentiation associated with inflammation. The Smad4 protein is the downstream mediator of TGF-beta. In this study, we examined the relationship between Smad4 expression and clinicopathological features in patients with hepatocellular carcinoma (HCC).
Expression of Smad4 was assessed in five HCC cell lines and in paired cancerous and noncancerous tissues in three patients with HCC, using Western blotting analysis. Moreover, Smad4 expression in 121 HCC patients was evaluated by using immunohistochemistry.
Only the Li7 and HT17 cell lines expressed the Smad4 protein. All human samples expressed the protein. Immunohistochemistry showed that Smad4 expression tended to be strong in small HCC nodules less than 45 mm in diameter (P=0.06) and in the infiltrated part of the tumor capsule. Postoperative survival analysis indicated that HCC patients with strong Smad4 expression had shorter disease-specific survival than those with weak expression (P=0.04). Multivariate analysis also showed that Smad4 expression could be one predictor of prognosis, but the correlation was not significant (P=0.07).
Although TGF-beta/Smad4 signaling may have various biological effects on human malignancies, strong Smad4 expression in HCC is likely to suggest poor prognosis. The information has implications for predicting HCC prognosis and developing targeted therapeutics.
转化生长因子-β（TGF-β）作为一种多效细胞因子，控制增殖、黏附和分化等功能，促进癌症的发生和抑制。此外，它与上皮-间充质转化过程和与炎症相关的 T 细胞分化有关。Smad4 蛋白是 TGF-β的下游介质。本研究检测了 Smad4 表达与肝细胞癌（HCC）患者临床病理特征的关系。
使用 Western blot 分析评估了 5 种 HCC 细胞系和 3 例 HCC 患者配对的癌组织和癌旁组织中 Smad4 的表达。此外，采用免疫组织化学法检测了 121 例 HCC 患者的 Smad4 表达。
仅 Li7 和 HT17 细胞系表达 Smad4 蛋白。所有人类样本均表达该蛋白。免疫组化显示，直径小于 45mm 的小 HCC 结节（P=0.06）和肿瘤包膜浸润部分的 Smad4 表达倾向较强。术后生存分析表明，Smad4 表达较强的 HCC 患者比表达较弱的患者疾病特异性生存时间更短（P=0.04）。多因素分析还表明，Smad4 表达可能是预后的一个预测因素，但相关性不显著（P=0.07）。
尽管 TGF-β/Smad4 信号通路可能对人类恶性肿瘤具有多种生物学效应，但 HCC 中 Smad4 表达较强可能提示预后不良。该信息对预测 HCC 预后和开发靶向治疗具有重要意义。
