title: Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) as a novel marker in T1 high-grade and T2 bladder cancer patients receiving neoadjuvant chemotherapy.
abstract: BACKGROUND
  To investigate associations between dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) expression and survival in T1 high-grade or T2 bladder cancer patients treated with neoadjuvant chemotherapy.
  
  
  METHODS
  The cohort under investigation comprised 44 patients who underwent neoadjuvant chemotherapy for pT1 high-grade or pT2N0M0 bladder cancer at our institution between 2002 and 2011. Immunohistochemical analysis was used to determine expression of DYRK2 in bladder cancer specimens obtained by transurethral resection before chemotherapy. Relationships between DYRK2 expression and both response to chemotherapy and survival in these patients were analyzed.
  
  
  RESULTS
  DYRK2 expression was positive in 21 of 44 patients (47.7 %) and negative in 23 patients (52.3 %). In total, 20 of 21 DYRK2-positive cases showed complete response to neoadjuvant chemotherapy, whereas 11 of 23 DYRK2-negative cases did not show complete response. Sensitivity and specificity were 62.5 % and 91.7 %, respectively (P = 0.0018). In addition, disease-specific survival rate was significantly higher for DYRK2-positive patients than for DYRK2-negative patients (P = 0.017). In multivariate analysis, DYRK2 expression level was identified as an independent prognostic factor for disease-specific survival (P = 0.029). We also showed that DYRK2 mRNA expression was significantly higher in DYRK2-positive samples by immunohistochemistry than DYRK2-negative samples (P = 0.040).
  
  
  CONCLUSIONS
  DYRK2 expression level may predict the efficacy of neoadjuvant chemotherapy for T1 high-grade and T2 bladder cancer.
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. shun1982@nms.ac.jp.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Nomura
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. yasu17@nms.ac.jp.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. s7053@nms.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. mterasaki@nms.ac.jp.
authors.forename: Mika
authors.initials: M
authors.lastname: Terasaki
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. s2027@nms.ac.jp.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kimata
authors.affiliation: Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. terasaki@nms.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Terasaki
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. hamasaki@nms.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. gokimura@nms.ac.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Kimura
authors.affiliation: Analytic Human Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. ashimizu@nms.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Departments of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. kondoy@nms.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kondo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D000097603:Dyrk Kinases
chemical_list: D014408:Biomarkers, Tumor; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases