Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer.
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.
Kusuda
Tomoyo
T
Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Shigemasa
Kazushi
K
Arihiro
Koji
K
Fujii
Tsuneo
T
Nagai
Nobutaka
N
Ohama
Koso
K
D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D021122:Protein Subunits; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma