The Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Liver Int. 2012 Jan;32(1):110-8. doi: 10.1111/j.1478-3231.2011.02619.x. Epub 2011 Aug 11.
Under hypoxia, tumour cells undergo genetic and adaptive changes that allow their survival. Previously, we reported that high expression of hypoxia-inducible factor (HIF)-1 was a significant predictive factor for recurrence in hepatocellular carcinoma (HCC). Hypoxia also stimulates expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) genes via the HIF-1 pathway.
The aim was to evaluate the relationship between hypoxia stress and expression of PLOD genes in HCC in vitro and to identify a new prognostic marker in HCC patients.
The PLOD2 expression was assessed under hypoxia in hepatoma cell lines and characterized in 139 HCC samples following hepatic resection using microarray experiments, quantitative RT-PCR and immunohistochemistry. Prognostic factors in HCC patients were assessed using univariate and multivariate analyses.
The PLOD2 expression was induced under the hypoxia in vitro. Disease-free survival in the high PLOD2 expression group of HCC patients was significantly shorter when compared with the low-expression group (P = 0.002). In a subset of HCCs, we found that the PLOD2 expression of microarray was correlated with data of quantitative RT-PCR and immunohistochemistry. Of clinicopathological factors, PLOD2 expression was significantly correlated with tumour size (P = 0.022) and macroscopic intrahepatic metastasis (P = 0.049). In univariate analysis, six prognostic factors (tumour multiplicity, macroscopic intrahepatic metastasis, histological grade, microscopic portal invasion, microscopic intrahepatic metastasis and PLOD2 expression) were significant for disease-free survival. PLOD2 expression was identified as a significant, independent factor of poor prognosis (P = 0.013).
PLOD2 is a potential novel prognostic factor for HCC patients following surgery.
在缺氧的情况下，肿瘤细胞会发生遗传和适应性变化，从而使其存活下来。我们之前曾报道过，缺氧诱导因子 (HIF)-1 的高表达是肝细胞癌 (HCC) 复发的一个重要预测因素。缺氧还通过 HIF-1 途径刺激脯氨酰-赖氨酸、2-氧戊二酸 5-双加氧酶 (PLOD) 基因的表达。
本研究旨在评估 HCC 细胞体外缺氧应激与 PLOD 基因表达的关系，并寻找 HCC 患者的新预后标志物。
在肝癌细胞系中评估缺氧条件下的 PLOD2 表达，并使用微阵列实验、定量 RT-PCR 和免疫组织化学方法在 139 例肝切除后的 HCC 样本中对其进行特征分析。使用单因素和多因素分析评估 HCC 患者的预后因素。
PLOD2 表达在体外缺氧条件下被诱导。与低表达组相比，高 PLOD2 表达组 HCC 患者的无病生存率明显缩短（P = 0.002）。在 HCC 的一个亚组中，我们发现微阵列的 PLOD2 表达与定量 RT-PCR 和免疫组织化学的数据相关。在临床病理因素中，PLOD2 表达与肿瘤大小（P = 0.022）和宏观肝内转移（P = 0.049）显著相关。在单因素分析中，肿瘤多发性、宏观肝内转移、组织学分级、镜下门静脉侵犯、镜下肝内转移和 PLOD2 表达等 6 个预后因素对无病生存率有显著影响。PLOD2 表达被确定为预后不良的独立危险因素（P = 0.013）。
PLOD2 是 HCC 患者手术后的一个有潜力的新预后因素。
