Elevated Plasma Growth Differentiation Factor-15 Correlates with Lymph Node Metastases and Poor Survival in Endometrial Cancer

Abstract

Purpose: The study objective was to investigate and validate plasma growth differentiation factor-15 (GDF-15) as a predictor of lymph node metastasis and a poor prognosis in primary endometrial cancer.Experimental Design: Plasma samples from 510 women treated for endometrial cancer in a primary investigation cohort (n ¼ 44) and a secondary validation cohort (n ¼ 466) were analyzed for GDF-15. Plasma from healthy premenopausal (n ¼ 20) and postmenopausal (n ¼ 20) women, women with borderline (n ¼ 43), benign (n ¼ 144), and malignant ovarian tumors (n ¼ 125) were used for comparison.Results: Median plasma GDF-15 concentration for the endometrial cancer group was elevated (1,077 ng/L) as compared with pre-and postmenopausal controls (590 and 684 ng/L) and women with benign (591 ng/L) or borderline ovarian tumors (718 ng/L; all P < 0.001), but similar to the ovarian cancer group. In the large validation cohort of endometrial carcinomas, high plasma GDF-15 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease, nonendometrioid histology, high grade, older age, postmenopausal status, and lymph node metastases (all P 0.001). High GDF-15 was also an independent predictor of poor disease-specific and recurrence-free survival.Conclusions: Based on findings indicated in a primary investigation set and confirmed in the large secondary validation set, we report for the first time plasma GDF-15 as a biomarker for endometrial cancer phenotype, including presence of lymph node metastasis and reduced survival. Its applicability as a predictor of metastatic nodes and in monitoring treatment of endometrial cancer needs to be further studied.

Bioactivity and Prognostic Significance of Growth Differentiation Factor GDF15 Secreted by Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma

“…The pGDF15 level increase was correlated with prognosis, as was reported for patients with prostate, colorectal, and endometrial cancers (27,28,48). Finally, we found a strong relation between pGDF15 level and survival to 30 months in patients with multiple myeloma.…”

Serum Carcinoembryonic Antigen as a Tumour Marker in Patients with Endometrial Cancer

“…Numerous studies have investigated biomarkers for endometrial cancer [1][2][3][4][5][6] . In particular, measurement of cancer antigen 125 (CA125) in serum has been investigated as a tumour marker in patients with endometrial cancer.…”

“…Although several biomarkers have been associated with clinical characteristics and prognosis in endometrial cancer [1][2][3][4][5][6] , none have been implemented in clinical practice. Novel biomarkers for endometrial cancer are therefore required.…”

CD8 down-regulation on cytotoxic T lymphocytes of patients with endometrioid endometrial carcinomas

“…GDF15 is a member of TGF-β superfamily [27] described as a marker of malignant phenotype of numerous tumors [28]. The serum levels of GDF15 occur during pregnancy [29] and, in patients with EC elevated plasma levels correlate with lymph node metastases and poor survival [30]. More studies are needed to determine whether CD8 down-regulation is directly or indirectly mediated by GDF15.…”