Cytokine gene expression signature in ovarian clear cell carcinoma

  • Authors:
    • Nozomu Yanaihara
    • Michael S. Anglesio
    • Kazunori Ochiai
    • Yukihiro  Hirata
    • Misato Saito
    • Chie Nagata
    • Yasushi Iida
    • Satoshi  Takakura
    • Kyosuke Yamada
    • Tadao Tanaka
    • Aikou Okamoto
  • View Affiliations

  • Published online on: June 26, 2012     https://doi.org/10.3892/ijo.2012.1533
  • Pages: 1094-1100
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Abstract

Cytokine expression in a tumor microenvironment can impact both host defense against the tumor and tumor cell survival. In this study, we sought to clarify whether the cytokine gene expression profile could have clinical associations with ovarian cancer. We analyzed the expression of 16 cytokine genes (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-γ, TNF-α, IL-6, HLA-DRA, HLA-DPA1 and CSF1) in 50 ovarian carcinomas. Hierarchical clustering analysis of these tumors was carried out using Cluster software and differentially expressed genes were examined between clear cell carcinoma (CCC) and other subtypes. Following this examination we evaluated the biological significance of IL-6 knockdown in CCC. Unsupervised hierarchical clustering analysis of cytokine gene expression revealed two distinct clusters. The relationship between the two clusters and clinical parameters showed statistically significant differences in CCC compared to other histologies. CCC showed a dominant Th-2 cytokine expression pattern driven largely by IL-6 expression. Inhibition of IL-6 in CCC cells suppressed Stat3 signaling and rendered cells sensitive to cytotoxic agents. The unique cytokine expression pattern found in CCC may be involved in the pathogenesis of this subtype. In particular, high IL-6 expression appears likely to be driven by the tumor cells, fueling an autocrine pathway involving IL-6 expression and Stat3 activation and may influence survival when exposed to cytotoxic chemotherapy. Modulation of IL-6 expression or its related signaling pathway may be a promising strategy of treatment for CCC.
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September 2012
Volume 41 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yanaihara N, Anglesio MS, Ochiai K, Hirata Y, Saito M, Nagata C, Iida Y, Takakura S, Yamada K, Tanaka T, Tanaka T, et al: Cytokine gene expression signature in ovarian clear cell carcinoma. Int J Oncol 41: 1094-1100, 2012.
APA
Yanaihara, N., Anglesio, M.S., Ochiai, K., Hirata, Y., Saito, M., Nagata, C. ... Okamoto, A. (2012). Cytokine gene expression signature in ovarian clear cell carcinoma. International Journal of Oncology, 41, 1094-1100. https://doi.org/10.3892/ijo.2012.1533
MLA
Yanaihara, N., Anglesio, M. S., Ochiai, K., Hirata, Y., Saito, M., Nagata, C., Iida, Y., Takakura, S., Yamada, K., Tanaka, T., Okamoto, A."Cytokine gene expression signature in ovarian clear cell carcinoma". International Journal of Oncology 41.3 (2012): 1094-1100.
Chicago
Yanaihara, N., Anglesio, M. S., Ochiai, K., Hirata, Y., Saito, M., Nagata, C., Iida, Y., Takakura, S., Yamada, K., Tanaka, T., Okamoto, A."Cytokine gene expression signature in ovarian clear cell carcinoma". International Journal of Oncology 41, no. 3 (2012): 1094-1100. https://doi.org/10.3892/ijo.2012.1533