Plasma growth differentiation factor-15 is an independent marker for aggressive disease in endometrial cancer.

Hilde Engerud,Kristine Eldevik Fasmer,Jone Trovik,Ingvild Løberg Tangen,Ingfrid Salvesen Haldorsen,Camilla Krakstad,Hege Fredriksen Berg,Kirsten Hope

doi:10.1371/journal.pone.0210585

Hilde Engerud, Kristine Eldevik Fasmer + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0210585

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Journal: PloS one	Publication Date: Jan 15, 2019
Citations: 7	License type: CC BY 4.0

Affiliation: University of Bergen, Haukeland University Hospital

Abstract

ObjectiveBetter biomarkers are needed in order to identify patients with endometrial carcinoma at risk of recurrence and who may profit from a more aggressive treatment regimen. Our objective was to explore the applicability of plasma growth differentiation factor 15 (GDF-15) as a marker for recurrent disease, as well as a marker for poor prognosis and lymph node metastases.MethodsEDTA-blood samples were obtained from 235 patients with endometrial cancer before primary surgery. For 36 of these patients, matching blood samples were collected at time of recurrence. Blood samples were also collected from 78 patients with endometrial hyperplasia. Plasma GDF-15 was measured by an enzyme-linked immunosorbent assay (ELISA). Preoperative pelvic MRI scans for 141 patients were investigated in parallel for imaging variables.ResultsPreoperative plasma level of GDF-15 was significantly higher for patients who experienced recurrence (1780 ng/L; 95% CI; 518–9475 ng/L) than for patients who did not develop recurrent disease (1236 ng/L; 95% CI; 307–7030 ng/L) (p<0.001). Plasma levels of GDF-15 at recurrence (2818 ng/L, 95% CI 2088–3548 ng/L) were significantly higher than plasma levels of GDF-15 measured at time of primary diagnosis (1857 ng/L, 95% CI; 1317–2398 ng/L) (p = 0.001). High plasma level GDF-15 independently predicts recurrent disease (OR = 3.14; 95% CI 2.10–4.76) and lymph node metastases (OR = 2.64; 95% CI 1.52–4.61). Patients with high plasma level of GDF-15 had significantly larger tumor volume (p = 0.008).ConclusionElevated plasma level of GDF-15 is associated with aggressive disease and lymph node metastasis in endometrial carcinoma. GDF-15 may be helpful in indicating recurrent disease.

Highlights

Endometrial cancer is the most common gynecologic malignancy and the fourth most common cancer among women in industrialised countries
Preoperative plasma level of growth differentiation factor 15 (GDF-15) was significantly higher for patients who experienced recurrence (1780 ng/L; 95% CI; 518–9475 ng/L) than for patients who did not develop recurrent disease (1236 ng/L; 95% CI; 307–7030 ng/L) (p
High plasma level GDF-15 independently predicts recurrent disease (OR = 3.14; 95% CI 2.10–4.76) and lymph node metastases (OR = 2.64; 95% CI 1.52–4.61)

Summary

Introduction

Endometrial cancer is the most common gynecologic malignancy and the fourth most common cancer among women in industrialised countries. The prognosis is good with an overall 5-year survival of 80%, 15–20% of patients with a presumed low risk disease experience recurrence [1]. To date there are no biomarkers for prognosis routinely available or in widespread use in the clinic and the majority of suggested markers have been developed for immunohistochemistry based detection in patient tissue biopsies. There has been little focus on identifying markers in preoperative blood samples [2,3,4]. Such markers are less invasive than those from biopsy, obtainable and could be measured repeatedly during the course of the disease. A robust prognostic plasma biomarker would potentially be highly valuable in the clinic

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Conclusion