Correlation of decreased survival and IL-18 in bone metastasis.
Correlation of decreased survival and IL-18 in bone metastasis.
复制标题
DOI：
10.2169/internalmedicine.48.1851
复制
发表时间：
2009
影响因子：
1.2
通讯作者：
M. Okamoto;K. Azuma;T. Hoshino;H. Imaoka;Jiro Ikeda;T. Kinoshita;S. Takamori;K. Ohshima;N. Edakuni;S. Kato;T. Iwanaga;H. Aizawa
中科院分区：
文献类型：
--
作者：
M. Okamoto;K. Azuma;T. Hoshino;H. Imaoka;Jiro Ikeda;T. Kinoshita;S. Takamori;K. Ohshima;N. Edakuni;S. Kato;T. Iwanaga;H. Aizawa
目的研究表明，某些肿瘤患者血清IL-18水平升高。我们研究了非小细胞肺癌（NSCLC）患者血清和癌细胞中IL-18的产生是否增加。检测79例患者的血清IFN-γ、IL-18和硫氧还蛋白1（TRX 1）水平（51例男性，28例女性，中位年龄67岁）腺癌57例，鳞癌22例; TNM分期IIIA [n=11]，IIIB [n=24]和IV [n=44]）和75名健康年龄匹配的对照组（44名男性，31名女性，中位年龄65岁）。我们用免疫组织化学方法检测了肺和腺癌骨转移部位IL-18的产生。结果NSCLC患者血清IL-18、IFN-γ和TRX 1水平显著高于对照组（分别为p<0.0001、p=0.0031和p<0.0001），而血清IFN-γ水平在NSCLC中略有升高。血清IL-18（而非IFN-γ或TRX 1）水平与NSCLC患者的总生存期显著相关（p=0.0102）且呈负相关。多因素生存分析显示血清IL-18水平是影响总生存率的独立预后因素。此外，血清IL-18水平显着（p=0.049）高于非小细胞肺癌骨转移比非小细胞肺癌骨转移。基于免疫组织化学，我们观察到肺和骨转移癌细胞显著产生IL-18。结论晚期NSCLC患者血清IL-18水平升高可能与肿瘤细胞产生IL-18有关。
OBJECTIVE Previous studies have reported that serum IL-18 levels are increased in some cancers. We investigated whether IL-18 production is increased in sera and cancer cells of patients with non-small cell lung cancer (NSCLC). PATIENTS OR MATERIALS Serum levels of IFN-gamma and IL-18 and thioredoxin 1 (TRX1) were measured in 79 patients (51 males, 28 females, median age 67 years) with advanced NSCLC (57 adenocarcinoma, 22 squamous cell carcinoma; TNM stages IIIA [n=11], IIIB [n=24], and IV [n=44]) and 75 healthy age-matched controls (44 males, 31 females, median age 65 years) by enzyme-linked immunosorbent assay. We examined IL-18 production in the lungs and sites of bone metastasis of adenocarcinoma by immunohistochemistry. RESULTS Serum IL-18, IFN-gamma, and TRX1 levels in NSCLC patients were significantly (p<0.0001, p=0.0031, and p<0.0001, respectively) higher than in control subjects, while serum IFN-gamma levels in NSCLC were slightly increased. Serum IL-18, but not IFN-gamma or TRX1, levels were significantly (p=0.0102) and negatively associated with overall survival in NSCLC. The serum IL-18 level was identified as an independent prognostic factor for overall survival in multivariate survival analysis. Moreover, serum IL-18 levels were significantly (p=0.049) higher in NSCLC with bone metastasis than in NSCLC without bone metastasis. Based on immunohistochemistry, we observed that cancer cells in the lungs and bone metastases markedly produced IL-18. CONCLUSION Our results suggest that elevated serum IL-18 levels may be associated with IL-18 producing cancer cells in advanced NSCLC.