title: Mutant GDF15 presents a poor prognostic outcome for patients with oral squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate the mutation status of growth differentiation factor 15 (GDF15) in patients with oral squamous cell carcinoma (OSCC), as well as the prognostic value of missense GDF15 mutations.
  
  
  METHODS
  Formalin-fixed paraffin-embedded biopsy samples from 46 OSCC patients were involved in this study. GDF15 and TP53 mutations were sequenced using the Ion Torrent Personal Genome Machine, GDF15 protein expression was detected using immunohistochemistry. Torrent Suite Software v.3.6, Integrative Genomics Viewer; v.2.3, statistical software SPSS18.0 for Windows were used for analysis. All hypothesis-generating tests were two-sided at a significance level of 0.05.
  
  
  RESULTS
  Twenty-nine GDF15 mutations were identified in 19 out of 46 patients (41.3%), including eighteen missense mutations, two nonsense mutations and nine synonymous mutations. The patients with missense GDF15 mutations had poorer prognostic outcomes than those with wild-type GDF15, including overall survival (P = 0.035), disease-free survival (P = 0.032), locoregional recurrence-free survival (P = 0.015), and distant metastasis-free survival (P = 0.070). Missense GDF15mutations was an independent increased risk factor of overall survival (HR = 5.993, 95% CI:1.856-19.346, P = 0.003), disease-free survival (HR = 3.764, 95% CI:1.295-10.945, P = 0.015), locoregional recurrence-free survival (HR = 4.555, 95% CI:1.494-13.889, P = 0.008), and distant metastasis-free survival (HR = 4.420, 95% CI:1.145-13.433, P = 0.009).
  
  
  CONCLUSIONS
  Patients with missense GDF15 mutations have significantly poorer outcomes than those with wild-type GDF15, missense GDF15 mutations could be used as an independent increased risk factor of poor prognosis in OSCC patients.
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Sun
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Tan
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Ma
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Dong-Wang
authors.initials: DW
authors.lastname: Zhu
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Wang
authors.affiliation: Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Yao-Yao
authors.initials: YY
authors.lastname: Tu
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Chen-Ping
authors.initials: CP
authors.lastname: Zhang
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
authors.forename: Lai-Ping
authors.initials: LP
authors.lastname: Zhong
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: growth differentiation factor 15; mutation; oral squamous cell carcinoma; prognosis