title: miR-34a is downregulated in cis-diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, Tohoku University School of Medicine, Miyagi, Japan. ogawa@orl.med.tohoku.ac.jp
authors.forename: Takenori
authors.initials: T
authors.lastname: Ogawa
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Saiki
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Shiga
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fukushige
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: Sho
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsuura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saijo
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Horii
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010255:Paranasal Sinus Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin