Yuan A, Yang P C, Yu C J, Chen W J, Lin F Y, Kuo S H, Luh K T
Departments of Internal Medicine, Surgery, and Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Am J Respir Crit Care Med. 2000 Nov;162(5):1957-63. doi: 10.1164/ajrccm.162.5.2002108.
Tumor-associated angiogenesis is important for tumor growth and metastasis. Interleukin (IL)-8 was recently reported to be an important angiogenic factor both in vitro and in vivo. In this study we evaluated, for the first time, IL-8 messenger RNA (mRNA) expression in non-small-cell lung cancer (NSCLC), using real-time quantitative reverse-transcription-polymerase chain reaction, and correlated IL-8 mRNA expression in tumor and nontumor lung samples from 58 patients with NSCLC (29 with squamous cell carcinoma and 29 with adenocarcinoma, of whom 20 had Stage I, 10 had Stage II, and 28 had Stage III disease) with these patients' clinicopathologic characteristics, angiogenesis, and outcome. IL-8 protein expression and tumor microvessel count (MC) were assessed immunohistochemically. IL-8 mRNA expression was significantly greater in tumor tissue; high expression was highly associated with tumor in advanced stages (p = 0.03), distant lymph node metastasis (p = 0.02), high tumor MC (> 123) (p = 0.00003), short survival (< 26 mo) (p < 0.00001), and early relapse (< 16 mo) (p < 0.00001). Tumor MC correlated strongly with IL-8 mRNA expression (r = 0.56, p < 0.001). Multivariate analysis showed IL-8 mRNA expression and intratumor MC to be the most important predictors of patient survival and relapse. Thus, in NSCLC, IL-8 mRNA expression is strongly associated with tumor progression, tumor angiogenesis, survival, and time to relapse, suggesting its use as a prognostic indicator.
肿瘤相关血管生成对肿瘤生长和转移至关重要。白细胞介素(IL)-8最近被报道在体外和体内均为重要的血管生成因子。在本研究中,我们首次采用实时定量逆转录-聚合酶链反应评估非小细胞肺癌(NSCLC)中IL-8信使核糖核酸(mRNA)的表达,并将58例NSCLC患者(29例鳞状细胞癌和29例腺癌,其中20例为Ⅰ期,10例为Ⅱ期,28例为Ⅲ期)肿瘤及非肿瘤肺组织样本中的IL-8 mRNA表达与这些患者的临床病理特征、血管生成及预后相关联。采用免疫组织化学方法评估IL-8蛋白表达和肿瘤微血管计数(MC)。肿瘤组织中IL-8 mRNA表达显著更高;高表达与晚期肿瘤(p = 0.03)、远处淋巴结转移(p = 0.02)、高肿瘤MC(> 123)(p = 0.00003)、短生存期(< 26个月)(p < 0.00001)及早期复发(< 16个月)(p < 0.00001)密切相关。肿瘤MC与IL-8 mRNA表达密切相关(r = 0.56,p < 0.001)。多变量分析显示IL-8 mRNA表达和肿瘤内MC是患者生存和复发的最重要预测指标。因此,在NSCLC中,IL-8 mRNA表达与肿瘤进展、肿瘤血管生成、生存及复发时间密切相关,提示其可作为一项预后指标。