Oncotarget

Clinical Research Papers:

Mutant GDF15 presents a poor prognostic outcome for patients with oral squamous cell carcinoma

Jie Ma, Xiao Tang, Wen-wen Sun, Ying Liu, Yi-ran Tan, Hai-long Ma, Dong-wang Zhu, Min Wang, Li-zhen Wang, Jiang Li, Yao-yao Tu, Chen-ping Zhang, Zhi-yuan Zhang and Lai-ping Zhong _

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Oncotarget. 2016; 7:2113-2122. https://doi.org/10.18632/oncotarget.6017

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Abstract

Jie Ma1,*, Xiao Tang1,*, Wen-wen Sun1, Ying Liu1, Yi-ran Tan1, Hai-long Ma1, Dong-wang Zhu1, Min Wang1, Li-zhen Wang2, Jiang Li2, Yao-yao Tu1, Chen-ping Zhang1, Zhi-yuan Zhang1, Lai-ping Zhong1

1Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China

2Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, China

*These authors have contributed equally to this work

Correspondence to:

Lai-ping Zhong, e-mail: zhonglp@hotmail.com

Yao-yao Tu, e-mail: tuyaoyao1117@163.com

Keywords: growth differentiation factor 15, mutation, oral squamous cell carcinoma, prognosis

Received: July 18, 2015     Accepted: October 06, 2015     Published: October 19, 2015

ABSTRACT

Purpose: 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.

Patients and 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.


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