Kusuda Tomoyo, Shigemasa Kazushi, Arihiro Koji, Fujii Tsuneo, Nagai Nobutaka, Ohama Koso
Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Oncol Rep. 2005 Jun;13(6):1153-8.
The aim of the present study was to examine mRNA expression levels of Th1 (TNF-alpha , IFN-gamma, and IL-12p40) and Th2 (IL-6 and IL-10) cytokines for any association with clinicopathological characteristics of epithelial ovarian cancer. mRNA was isolated, and cDNA prepared from 40 samples of epithelial ovarian cancers. Expression level of each cytokine mRNA was examined by the real-time PCR technique (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate gene expression. Results were analyzed against clinical stage, histological grade, and histological type. Prognostic significance of expression levels of each combination of Th1/Th2 values was assessed. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) expression levels were significantly higher in serous adenocarcinoma than in non-serous adenocarcinoma (p<0.05), but with no difference between individual cytokine mRNA expression levels and clinical stage or histological grade. Log-rank testing showed that high TNF-alpha mRNA expression (p=0.033) and the diameter of largest residual lesion at initial surgery (p=0.012) significantly correlate with longer survival in advanced stage (II/III/IV) ovarian carcinomas. In examining all combinations of Th1/Th2 expression values, the most significant association was between high IFN-gamma.IL-12p40/IL-6 expression levels and better prognosis in advanced stage (II/III/IV) ovarian carcinomas (p=0.004). In multivariate analysis, high IFN-gamma.IL-12p40/IL-6 expression (p=0.009) and the diameter of residual lesion (p=0.011) remained significantly associated with survival, whereas high TNF-alpha expression lost significance. In conclusion, Th1 and Th2 cytokines might play an important role in regulating the immune reaction in epithelial ovarian cancer cells. IFN-gamma.IL-12p40/IL-6 expression may be a useful prognostic molecular marker for patients with advanced ovarian cancer.
本研究的目的是检测Th1（肿瘤坏死因子-α、干扰素-γ和白细胞介素-12p40）和Th2（白细胞介素-6和白细胞介素-10）细胞因子的mRNA表达水平，以探讨其与上皮性卵巢癌临床病理特征之间的关系。从40例上皮性卵巢癌样本中分离出mRNA，并制备cDNA。采用实时PCR技术（以甘油醛-3-磷酸脱氢酶基因作为内对照）检测各细胞因子mRNA的表达水平。用表达率（目的基因/甘油醛-3-磷酸脱氢酶）评估基因表达。将结果与临床分期、组织学分级和组织学类型进行分析。评估Th1/Th2值各组合的表达水平的预后意义。浆液性腺癌中肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的表达水平显著高于非浆液性腺癌（p<0.05），但各细胞因子mRNA表达水平与临床分期或组织学分级之间无差异。对数秩检验显示，在晚期（II/III/IV期）卵巢癌中，高TNF-α mRNA表达（p=0.033）和初次手术时最大残留病灶直径（p=0.012）与较长生存期显著相关。在检测Th1/Th2表达值的所有组合时，最显著的关联是晚期（II/III/IV期）卵巢癌中高IFN-γ·IL-12p40/IL-6表达水平与较好预后之间的关联（p=0.004）。多因素分析显示，高IFN-γ·IL-12p40/IL-6表达（p=0.009）和残留病灶直径（p=0.011）仍与生存期显著相关，而高TNF-α表达则失去显著性。总之，Th1和Th2细胞因子可能在上皮性卵巢癌细胞免疫反应调节中起重要作用。IFN-γ·IL-12p40/IL-6表达可能是晚期卵巢癌患者有用的预后分子标志物。
