Ma Jie, Tang Xiao, Sun Wen-Wen, Liu Ying, Tan Yi-Ran, Ma Hai-Long, Zhu Dong-Wang, Wang Min, Wang Li-Zhen, Li Jiang, Tu Yao-Yao, Zhang Chen-Ping, Zhang Zhi-Yuan, Zhong Lai-Ping
Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China.
Oncotarget. 2016 Jan 12;7(2):2113-22. doi: 10.18632/oncotarget.6017.
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.
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.
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).
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.
研究生长分化因子15（GDF15）在口腔鳞状细胞癌（OSCC）患者中的突变状态，以及错义GDF15突变的预后价值。
本研究纳入了46例OSCC患者的福尔马林固定石蜡包埋活检样本。使用Ion Torrent个人基因组测序仪对GDF15和TP53进行测序，采用免疫组织化学法检测GDF15蛋白表达。使用Torrent Suite Software v.3.6、Integrative Genomics Viewer v.2.3以及Windows版统计软件SPSS18.0进行分析。所有假设生成检验均为双侧检验，显著性水平为0.05。
在46例患者中的19例（41.3%）中鉴定出29个GDF15突变，包括18个错义突变、2个无义突变和9个同义突变。错义GDF15突变患者的预后结果比野生型GDF15患者差，包括总生存期（P = 0.035）、无病生存期（P = 0.032）、局部区域无复发生存期（P = 0.015）和远处转移无复发生存期（P = 0.070）。错义GDF15突变是总生存期（HR = 5.993，95%CI：1.856 - 19.346，P = 0.003）、无病生存期（HR = 3.764，95%CI：1.295 - 10.945，P = 0.015）、局部区域无复发生存期（HR = 4.555，95%CI：1.494 - 13.889，P = 0.008）和远处转移无复发生存期（HR = 4.420，95%CI：1.145 - 13.433，P = 0.009）的独立风险增加因素。
错义GDF15突变患者的预后明显比野生型GDF15患者差，错义GDF15突变可作为OSCC患者预后不良的独立风险增加因素。
