GDF15 predict platinum response during first-line chemotherapy and can act as a complementary diagnostic serum biomarker with CA125 in epithelial ovarian cancer

Dan Zhao,Xiaobing Wang,Wei Zhang

doi:10.1186/s12885-018-4246-4

Dan Zhao, Xiaobing Wang + Show 1 more

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https://doi.org/10.1186/s12885-018-4246-4

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Abstract

BackgroundGrowth differentiation factor 15 (GDF15) has attracted much interest as a novel biomarker for epithelial ovarian carcinoma (EOC). Research focus has been directed at GDF15 as a diagnostic detection, while the prognostic determination of GDF15 in EOC patients remains to be clearly elucidated. The present study aimed to investigate GDF15 level relative to clinicopathological characters, chemoresponse, and clinical outcome of EOC patients.MethodsSerum from 122 patients with primary diagnosed EOC were analyzed for GDF15 and serum cancer antigen 125 (CA125). All cases were treated with debulking surgery and first-line chemotherapy, and samples were obtained just before debulking surgical treatment and first-line chemotherapy. Subsequently, clinical characteristics, responses to chemotherapy and progression-free survival (PFS) were recorded.ResultsIncreasing levels of serum GDF15 was significantly associated with FIGO stage and lymphonodus metastasis. GDF15 and CA125 detection are complementary in the diagnosis of EOC and can be simultaneously profiled. The chemo-resistant EOC patients (median, 1225.0 pg/mL) showed significantly higher GDF15 than chemo-sensitive patients (median, 824.2 pg/mL; P = 0.013). Highly expressed GDF15 was an independent negative prognostic indicator in the PFS (P = 0.026) of the 122 EOC cases in the multivariate analysis. Additionally, patients with high level of serum CA125 significantly associated with suboptimal (P = 0.043) debulking surgery.ConclusionsOur results provide valuable evidence that GDF15 is related with first-line chemo-resistance, with highly expressed GDF15 being a strong and an independent indicator of shorter PFS in EOC patients.

Highlights

Growth differentiation factor 15 (GDF15) has attracted much interest as a novel biomarker for epithelial ovarian carcinoma (EOC)
Elevated levels of serum GDF15 and cancer antigen 125 (CA125) were noticeable in EOC We detected increased levels of GDF15 in the pretreatment serum of EOC patients compared with healthy subjects
The serum GDF15 levels varied and gradually increased with Federation of International of Gynecology and Obstetrics (FIGO) stage, in particular, the level of GDF15 in stage I-II EOC patient (604.6 pg/mL, p = 0.018) was significantly increased in comparison with healthy controls, suggesting that the increased serum GDF15 might present in the early stage of EOC

Summary

Introduction

Growth differentiation factor 15 (GDF15) has attracted much interest as a novel biomarker for epithelial ovarian carcinoma (EOC). The present study aimed to investigate GDF15 level relative to clinicopathological characters, chemoresponse, and clinical outcome of EOC patients. The prediction of patient with EOC who is resistant to first-line chemotherapy can allow making the correct selection of drugs that function via other mechanisms, and discovery of novel therapeutic strategies. A consensus has not yet been reached in predicting chemotherapy sensitivity and survival by preoperative serum CA125 level in patients with EOC [7,8,9,10]. As the tumor biomarkers for predicting chemo-resistance remains limited, the determination of novel biomarkers will be beneficial in strengthening surveillance of the disease and make reasonable clinical decisions, presenting the best opportunity for successful treatment and improved outcome

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