Combined functional genome survey of therapeutic targets for clear cell carcinoma of the kidney

Hideaki Ito, Kazufumi Honda, Reiko Satow, Eri Arai, Miki Shitashige, Masaya Ono, Tomohiro Sakuma, Shigeru Sakano, Katsusuke Naito, Hideyasu Matsuyama, Tesshi Yamada

Research output: Contribution to journalArticle

Abstract

Objective: Emerging molecular targeting therapeutics have been incorporated into the management of advanced renal cell carcinoma; however, their efficacy remains limited. The aim of this study was to catalog potential therapeutic target molecules for renal cell carcinoma. Methods: We first selected genes up-regulated in clear cell renal cell carcinoma relative to surrounding normal kidney tissues in 10 patients (Study Cohort) using high-density exon arrays that detect all potential transcripts predicted in the human genome. The selected genes were subjected to independent validation in another set of 10 patients (Validation Cohort) using real-time reverse transcriptase polymerase chain reaction and functional screening using small interfering RNA in six clear cell renal cell carcinoma cell lines. Results: We identified 164 genes whose expression was significantly elevated in clear cell renal cell carcinoma (P < 0.0001 [Student's t-test] and at least a 3-fold change in transcription signal). We finally extracted 33 genes required for maintaining cell proliferation in at least two clear cell renal cell carcinoma cell lines. The 33 genes included 13 genes known to be associated with the development/progression of renal cell carcinoma, including CAIX and FLT-1, confirming the robustness of the current strategy. Conclusions: Through a combination of genome-wide expression and functional assays, we identified a set of genes with high potential as targets for drug development. This method is rapid and comprehensive and could be applied to the discovery of diagnostic biomarkers and therapeutic targets for cancers other than clear cell renal cell carcinoma.

Original languageEnglish
Article numberhyr060
Pages (from-to)847-853
Number of pages7
JournalJapanese Journal of Clinical Oncology
Volume41
Issue number7
DOIs
Publication statusPublished - 2011 Jul
Externally publishedYes

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Keywords

  • Exon array
  • Functional screening
  • Molecular targeting therapy
  • Renal cell carcinoma
  • Small interfering RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Radiology Nuclear Medicine and imaging

Cite this

Ito, H., Honda, K., Satow, R., Arai, E., Shitashige, M., Ono, M., Sakuma, T., Sakano, S., Naito, K., Matsuyama, H., & Yamada, T. (2011). Combined functional genome survey of therapeutic targets for clear cell carcinoma of the kidney. Japanese Journal of Clinical Oncology, 41(7), 847-853. [hyr060]. https://doi.org/10.1093/jjco/hyr060