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肝细胞生长因子和白细胞介素-8 的共表达导致原发性鼻咽癌患者预后不良。

Co-elevated expression of hepatocyte growth factor and Interleukin-8 contributes to poor prognosis of patients with primary nasopharyngeal carcinoma.

机构信息

Department of Pathology, 1st Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.

出版信息

Oncol Rep. 2010 Jan;23(1):141-50.

Abstract

Hepatocyte growth factor (HGF) related tumor angiogenesis and prognosis of patients with nasopharyngeal carcinoma (NPC) has not been identified. The expressions of HGF and IL-8, as well as microvessels density were evaluated in 127 NPC biopsies by immunohistochemical staining. The correlation between these parameters and patient's clinicopathological features was analyzed statistically. In vitro, IL-8 concentration was evaluated in exogenous HGF-treated NPC cell lines by ELISA assay. The presence of EBV was also detected in NPC cells by PCR for Bam HI-W fragment. Both 54.3% (69/127) cases of HGF high-expression in tumor cells and 80.3% (102/127) of HGF high-expression in stromal cells were significantly associated with increased microvessels density, advanced clinical stage, lymph node metastasis and high-expression of IL-8. Angiogenesis exhibited in relation to overall survival of NPC patients (P=0.001), and the patients with HGF and IL-8 dual high-expression tumors had a significantly worse prognosis than those with single protein high-expression and dual low expression tumors (P=0.011 and P=0.026, respectively). Exogenous HGF was observed to promote induction of IL-8 in NPC cells without EBV infection. Co-operating with IL-8, HGF might contribute to a poor prognosis of NPC by inducing angiogenesis through both autocrine and paracrine EBV-independent pathways.

摘要

肝细胞生长因子(HGF)与鼻咽癌(NPC)患者的肿瘤血管生成和预后的关系尚未确定。通过免疫组织化学染色,评估了 127 例 NPC 活检标本中 HGF 和白细胞介素 8(IL-8)的表达以及微血管密度。统计分析了这些参数与患者临床病理特征之间的相关性。在体外,通过 ELISA 测定外源性 HGF 处理的 NPC 细胞系中的 IL-8 浓度。通过 PCR 检测 EBV 在 NPC 细胞中的存在,针对 Bam HI-W 片段。肿瘤细胞中 HGF 高表达的病例(69/127,54.3%)和基质细胞中 HGF 高表达的病例(102/127,80.3%)均与微血管密度增加、临床分期较晚、淋巴结转移和 IL-8 高表达显著相关。血管生成与 NPC 患者的总生存相关(P=0.001),并且 HGF 和 IL-8 双重高表达肿瘤的患者比单种蛋白高表达和双重低表达肿瘤的患者预后明显更差(P=0.011 和 P=0.026)。观察到外源性 HGF 促进了无 EBV 感染的 NPC 细胞中 IL-8 的诱导。HGF 与 IL-8 协同作用,通过自分泌和旁分泌 EBV 非依赖性途径诱导血管生成,可能导致 NPC 的不良预后。

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