Original Article

miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis

  1. Takenori Ogawa1,2,*,
  2. Yuriko Saiki1,
  3. Kiyoto Shiga2,
  4. Na Chen1,
  5. Shinichi Fukushige1,
  6. Makoto Sunamura1,3,
  7. Hiroki Nagase4,
  8. Sho Hashimoto5,
  9. Kazuto Matsuura6,
  10. Shigeru Saijo6,
  11. Toshimitsu Kobayashi2,
  12. Akira Horii1,*

Article first published online: 6 JUL 2012

DOI: 10.1111/j.1349-7006.2012.02338.x

Issue

Cancer Science

Cancer Science

Volume 103, Issue 9, pages 1737–1743, September 2012

Additional Information

How to Cite

(Cancer Sci, 2012; 103: 1737–1743)

Author Information

  1. 1

    Department of Molecular Pathology, Tohoku University School of Medicine, Miyagi, Japan

  2. 2

    Department of Otolaryngology and Head and Neck Surgery, Tohoku University School of Medicine, Miyagi, Japan

  3. 3

    Department of Digestive Tract Surgery and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan

  4. 4

    Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan

  5. 5

    Department of Otolaryngology and Head and Neck Surgery, National Hospital Organization Sendai Medical Center, Miyagi, Japan

  6. 6

    Division of Head and Neck Surgery, Miyagi Cancer Center, Miyagi, Japan

* To whom correspondence should be addressed.
E-mails: ogawa@orl.med.tohoku.ac.jp; horii@med.tohoku.ac.jp

Publication History

  1. Issue published online: 3 SEP 2012
  2. Article first published online: 6 JUL 2012
  3. Accepted manuscript online: 24 MAY 2012 12:00AM EST
  4. Manuscript Accepted: 21 MAY 2012
  5. Manuscript Revised: 14 MAY 2012
  6. Manuscript Received: 12 JAN 2012

Funded by

  • Academic Frontier Project for Private Universities
  • Ministry of Education, Culture, Sports, Science and Technology of Japan
  • Ministry of Health, Labour and Welfare of Japan

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For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of miR-34a and poor disease specific survival (P = 0.0015), poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between miR-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.00–0.29, P = 0.011) and local control rate at 0.008 (95% CI 0.00–0.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that miR-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum.

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