National Cancer Institute G. Pascale Foundation-Oncology Research Center of Mercogliano (CROM), Mercogliano, Italy.
Oncol Rep. 2013 Jun;29(6):2163-8. doi: 10.3892/or.2013.2378. Epub 2013 Apr 3.
The detection and diagnosis of hepatocellular carcinoma (HCC) at an early stage may significantly affect the prognosis of HCC patients. Thus, it is necessary to always identify novel putative markers for improving diagnosis. Hepatocarcinogenesis correlates with pathological hepatic angiogenesis. However, each tumor-induced angio-genetic process is influenced by the microenvironment through several pro- and anti-angiogenic factors released from tumor cells, tumor-associated inflammatory cells and/or from the extracellular matrix, and modulated by various signal pathways. In this study, we evaluated the profiling of angiogenic factors using Bio-Plex Pro™ Human Cancer Biomarker Panel 1, a 16-plex magnetic bead-based assay, in sera of patients with chronic hepatitis C (CHC) virus, liver cirrhosis (LC) and HCC. Our results demonstrated: i) high levels of hepatocyte growth factor (HGF) and prolactin only in LC and HCC patients, ii) high levels of soluble human epidermal growth factor receptor‑2 (sHER-2/neu; ErbB-2), sIL-6Ra, leptin (LEP) and platelet endothelial cell adhesion molecule‑1 (PECAM-1) in CHC, LC and HCC patients and iii) that sIL-6R correlated with the fibrosis stage in CHC patients, with Child‑Pugh score in those patients with LC and with tumor size in those patients with HCC, confirming that this protein may be used as a predictor of liver damage and of inflammatory process leading to fibrosis, cirrhosis, and subsequently to cancer. Moreover, an interactomic study conducted using the Ingenuity Pathway Analysis (IPA) software proved the existence of a correlation between 5 significant proteins [ErbB-2, sIL-6Ra, prolactin (PRL), HGF and LEP] which are involved in the same metabolic pathways.
早期检测和诊断肝细胞癌 (HCC) 可能显著影响 HCC 患者的预后。因此，有必要不断发现新的潜在标志物以改善诊断。肝癌发生与病理性肝血管生成有关。然而，每个肿瘤诱导的血管生成过程都受到肿瘤细胞、肿瘤相关炎症细胞和/或细胞外基质释放的几种促血管生成和抗血管生成因子的影响，并通过各种信号通路进行调节。在这项研究中，我们使用 Bio-Plex Pro ™ Human Cancer Biomarker Panel 1（一种 16 plex 基于磁珠的检测方法）评估了慢性丙型肝炎病毒 (CHC) 、肝硬化 (LC) 和 HCC 患者血清中血管生成因子的谱。我们的结果表明：i）仅在 LC 和 HCC 患者中 HGF 和催乳素水平升高，ii）CHC、LC 和 HCC 患者中可溶性人表皮生长因子受体-2 (sHER-2/neu; ErbB-2)、sIL-6Ra、瘦素 (LEP) 和血小板内皮细胞黏附分子-1 (PECAM-1) 水平升高，iii）sIL-6R 与 CHC 患者的纤维化分期相关，与 LC 患者的 Child-Pugh 评分相关，与 HCC 患者的肿瘤大小相关，证实该蛋白可用作肝损伤和炎症过程的预测因子，导致纤维化、肝硬化，随后导致癌症。此外，使用 Ingenuity Pathway Analysis (IPA) 软件进行的相互作用组学研究证明了 5 种显著蛋白 [ErbB-2、sIL-6Ra、催乳素 (PRL)、HGF 和 LEP] 之间存在相关性，它们参与了相同的代谢途径。
