title: Elevated level of serum growth differentiation factor 15 is associated with oral leukoplakia and oral squamous cell carcinoma.
abstract: BACKGROUND
  Although molecular mechanism of growth differentiation factor 15 (GDF15) in tumorigenesis of oral squamous cell carcinoma (OSCC) is not clear, the diagnostic and prognostic value of serum GDF15 detection has been noticed. However, serum GDF15 levels in patients with oral leukoplakia and GDF15 as a potential predictive biomarker for response to induction chemotherapy in patients with OSCC have not been reported.
  
  
  METHODS
  Pretreatment serum GDF15 concentration was detected using an enzyme-linked immunosorbent assay in 30 healthy persons, 24 patients with oral leukoplakia, and 60 patients with OSCC.
  
  
  RESULTS
  Serum GDF15 concentration was significantly higher in patients with oral leukoplakia and OSCC, compared with healthy controls (F = 13.701, df = 2, P < 0.001). From a diagnostic standpoint, a cutoff value of 346.9 ng/l of serum GDF15 concentration was calculated using receiver operating characteristic curve, with a sensitivity of 0.750, specificity of 0.867, Youden's Index of 0.617, and area under curve of 0.863. From a prognostic standpoint, patients with serum GDF15 concentration <346.9 ng/l had an improved 3-year disease-free survival rate (64.3% vs 56.5%) compared with those above 346.9 ng/l, but the difference was not statistically significant. A decreased concentration of GDF15 (<346.9 ng/l) showed a predictive trend toward an improved response to induction chemotherapy compared with elevated concentration with clinical response rates of 100% and 71.4%, respectively, but the difference was not significant.
  
  
  CONCLUSIONS
  Elevated GDF15 level may be not only a diagnostic biomarker for oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC.
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cheng-Zhe
authors.initials: CZ
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Qing-Qiong
authors.initials: QQ
authors.lastname: Luo
authors.forename: David M
authors.initials: DM
authors.lastname: Neskey
authors.forename: Dong-Wang
authors.initials: DW
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.forename: Chen-Ping
authors.initials: CP
authors.lastname: Zhang
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Lai-Ping
authors.initials: LP
authors.lastname: Zhong
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000556:secondary / Q000601:surgery; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D060828:Induction Chemotherapy; D007972:Leukoplakia, Oral / Q000097:blood* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood* / Q000601:surgery; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: growth differentiation factor 15; induction chemotherapy; oral leukoplakia; oral squamous cell carcinoma; serum