Chun Yun Shin, Huang Min, Rink Lori, Von Mehren Margaret
Hepato-Pancreato-Biliary Programs, Virginia Piper Cancer Institute, 800 E, 28th Street, Suite 602, Minneapolis, MN 55407, USA.
World J Surg Oncol. 2014 Jul 22;12:231. doi: 10.1186/1477-7819-12-231.
The insulin-like growth factor (IGF) pathway is implicated in the pathogenesis of hepatocellular carcinoma (HCC) and may be important in nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine expression levels of IGFs and receptors in NAFLD-associated HCC.
Tissue microarrays were constructed from patients who underwent hepatectomy for HCC. Immunohistochemistry was performed using antibodies for IGF ligands and receptors. Immunostain results were scored by a pathologist blinded to clinical data.
Among 27 patients with HCC, the most common underlying liver diseases included NAFLD, hepatitis C, and alcoholic hepatitis. Expression levels of IGFs and receptors were not associated with patients' underlying liver disease. In all patients, IGF-2 expression was upregulated in tumor and adjacent non-neoplastic liver. Expression of IGF-1 was low in adjacent liver in 6 of 10 patients with cirrhosis, compared with 2 of 17 patients without cirrhosis (P = 0.025). Higher IGF-1 expression in liver adjacent to tumor was associated with poorer median survival of 22 months, compared with 72 months with equal or lower IGF-1 expression in adjacent liver relative to tumor (P = 0.006).
Our preliminary results demonstrate significant associations between IGF-1 expression and liver cirrhosis and survival after resection in patients with HCC, independent of their underlying liver disease.
胰岛素样生长因子（IGF）通路与肝细胞癌（HCC）的发病机制有关，在非酒精性脂肪性肝病（NAFLD）中可能也很重要。本研究旨在确定NAFLD相关HCC中IGF及其受体的表达水平。
从因HCC接受肝切除术的患者中构建组织芯片。使用针对IGF配体和受体的抗体进行免疫组织化学检测。免疫染色结果由一位对临床数据不知情的病理学家进行评分。
在27例HCC患者中，最常见的潜在肝脏疾病包括NAFLD、丙型肝炎和酒精性肝炎。IGF及其受体的表达水平与患者潜在的肝脏疾病无关。在所有患者中，IGF-2在肿瘤及相邻的非肿瘤性肝脏中表达上调。10例肝硬化患者中有6例相邻肝脏中IGF-1表达较低，而17例非肝硬化患者中有2例出现这种情况（P = 0.025）。肿瘤相邻肝脏中IGF-1表达较高与较差的中位生存期相关，中位生存期为22个月，而相邻肝脏中IGF-1表达等于或低于肿瘤的患者中位生存期为72个月（P = 0.006）。
我们的初步结果表明，IGF-1表达与HCC患者的肝硬化及切除术后生存率之间存在显著关联，且独立于其潜在的肝脏疾病。
