伴有肝硬化的肝细胞癌中的缺氧诱导因子1α：与预后的关联。

Hypoxia inducible factor 1α in hepatocellular carcinoma with cirrhosis: Association with prognosis.

作者信息

Wang Dan, Zhang Xiaojing, Lu Yapeng, Wang Xueting, Zhu Li

机构信息

Institute for Nautical Medicine, Nantong University, Nantong, Jiangsu 226019, China.

Core Facility Molecular Pathology and Biobanking at the Department of Clinical Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China; Medical School of Nantong University, Nantong, Jiangsu, 226001, China.

出版信息

Pathol Res Pract. 2018 Dec;214(12):1987-1992. doi: 10.1016/j.prp.2018.09.007. Epub 2018 Sep 13.

DOI:10.1016/j.prp.2018.09.007

PMID:30274686

Abstract

BACKGROUND

Hypoxia inducible factor 1α (HIF-1α) is a protein related with carcinogenesis and metastasis in many tumors. However, little is known about the prognostic value of HIF-1α in hepatocellular carcinoma (HCC) patients with cirrhosis.

METHODS

Clinical-pathological information and follow-up data were collected from HCC (n = 419) and chronic hepatitis (n = 49) patients. HIF-1α expression was scored based on the percentage of immunohistochemical staining. Correlations between HIF-1α expression and clinical features were evaluated by Chi-square test. And survival analysis was performed by multivariate Cox regression analysis.

RESULTS

In cirrhosis patients, the frequency of HIF-1α positive expression in HCC was higher than in chronic hepatitis (P = 0.002). HIF-1α positive expression was significantly associated with vascular invasion (P = 0.002), TNM stage (P = 0.005), HBV infection (P = 0.005), tumor size (P = 0.025) and portal vein tumor thrombus (P = 0.001) in HCC with liver cirrhosis. While, in cirrhosis-free patients, HIF-1α positive expression had a significant correlation with vascular invasion (P = 0.039) and AFP value (P = 0.001) in. HIF-1α "positive" had decreased overall survival compared to HIF-1α "negative" patients and this was an independent adverse prognostic factor (multivariable analysis P = 0.001) for HCC patients with cirrhosis, but not for cirrhosis-free patients.

CONCLUSIONS

Our results suggested that HIF-1α served as a poor prognostic factor for HCC patients with cirrhosis.

摘要

背景

缺氧诱导因子1α（HIF-1α）是一种与多种肿瘤的发生和转移相关的蛋白质。然而，关于HIF-1α在肝硬化肝细胞癌（HCC）患者中的预后价值知之甚少。

方法

收集HCC患者（n = 419）和慢性肝炎患者（n = 49）的临床病理信息及随访数据。基于免疫组化染色百分比对HIF-1α表达进行评分。采用卡方检验评估HIF-1α表达与临床特征之间的相关性。通过多变量Cox回归分析进行生存分析。

结果

在肝硬化患者中，HCC患者HIF-1α阳性表达频率高于慢性肝炎患者（P = 0.002）。在伴有肝硬化的HCC中，HIF-1α阳性表达与血管侵犯（P = 0.002）、TNM分期（P = 0.005）、HBV感染（P = 0.005）、肿瘤大小（P = 0.025）及门静脉癌栓（P = 0.001）显著相关。而在无肝硬化患者中，HIF-1α阳性表达与血管侵犯（P = 0.039）及AFP值（P = 0.001）显著相关。与HIF-1α“阴性”患者相比，HIF-1α“阳性”患者的总生存期缩短，这是伴有肝硬化的HCC患者的独立不良预后因素（多变量分析P = 0.001），但在无肝硬化患者中并非如此。