Mount Sinai Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Gastroenterology. 2013 May;144(5):1024-30. doi: 10.1053/j.gastro.2013.01.021. Epub 2013 Jan 17.
BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC.
We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC.
Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively.
A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.
肝硬化影响全球 1%至 2%的人口，是肝细胞癌（HCC）的主要危险因素。丙型肝炎肝硬化相关 HCC 是美国癌症死亡人数增长最快的原因。已经开发了非侵入性方法来识别无症状早期肝硬化患者，增加了 HCC 监测的负担，但需要生物标志物来识别最需要监测的肝硬化患者。我们研究了以前与 HCC 患者的预后相关的肝脏衍生的 186 个基因特征是否对新诊断为肝硬化但无 HCC 的患者具有预后意义。
我们对意大利中心前瞻性随访中位数为 10 年的 216 例丙型肝炎相关早期（Child-Pugh 分级 A）肝硬化患者的肝针活检标本进行了基因表达谱分析。我们评估了 186 个基因特征是否与死亡、肝硬化进展和 HCC 发展相关。
55（25%）、101（47%）和 60（28%）例患者分别被归类为预后不良、中间预后和良好预后。在多变量 Cox 回归模型中，预后不良特征与死亡（P=0.004）、进展为晚期肝硬化（P<0.001）和 HCC 发展（P=0.009）显著相关。10 年生存率分别为 63%、74%和 85%，预后不良、中间预后和良好预后患者的 HCC 年发生率分别为 5.8%、2.2%和 1.5%。
用于预测 HCC 患者预后的 186 个基因特征也与丙型肝炎相关早期肝硬化患者的预后相关。该特征可能用于识别最需要监测的肝硬化患者，并制定预防 HCC 发展的策略。
