*Department of Obstetrics and Gynecology, Haukeland University Hospital, and †Department of Clinical Medicine, The University of Bergen, Bergen, Norway; ‡Gynecologic Oncology, University Hospitals Leuven, Leuven, Belgium; §Gynecologic Oncology, University Hospitals Leuven & Department of Oncology, KU Leuven, Leuven, Belgium; ∥Department of Gynecology, Oslo University Hospital, Ulleval, and ¶Faculty of Medicine, University of Oslo, Oslo, Norway.
Int J Gynecol Cancer. 2014 Feb;24(2):252-9. doi: 10.1097/IGC.0000000000000037.
The aim of this study was to investigate and validate circulating growth differentiation factor-15 (GDF-15) as a discriminating biomarker between highly malignant uterine sarcomas and benign uterine leiomyomas. In addition, we investigated whether GDF-15 differed between uterine sarcomas and benign adnexal tumors, ovarian or endometrial cancer, and borderline tumors of the ovary.
Preoperative blood samples from 19 women with a diagnosis of uterine sarcoma were analyzed for GDF-15 with immunoassay and compared with samples from 50 patients operated on for leiomyoma uteri and with samples from 20 premenopausal and 20 postmenopausal controls. Our previously presented preoperative GDF-15 concentrations in women with borderline (n = 43), benign (n = 144), and malignant ovarian tumors (n = 125), as well as endometrial cancer (n = 510), were used for comparison.
The median circulating GDF-15 concentration was elevated in the uterine sarcoma group (943 ng/L) compared with the myoma uteri group (647 ng/L), the premenopausal and postmenopausal controls (363 and 545 ng/L), and the women with benign ovarian tumors (591 ng/L, all P ≤ 0.007) but was not significantly different from the ovarian borderline tumor (718 ng/L) or ovarian (1242 ng/L) or endometrial cancer (1076 ng/L) groups.High GDF-15 levels were significantly associated with leiomyosarcomas (P = 0.036), advanced disease (International Federation of Gynecology and Obstetrics stage III/IV, P = 0.013), large tumors (≥10 cm, P = 0.009), and poor survival (P = 0.022).
Circulating GDF-15 may be a promising novel biomarker for the preoperative identification of malignant pelvic disease. Further large prospective studies are needed to evaluate the clinical usefulness of GDF-15 as a discriminator between benign leiomyomas and aggressive sarcomas and as a marker to guide surgical and systemic therapy.
本研究旨在探讨和验证循环生长分化因子 15（GDF-15）作为区分高度恶性子宫肉瘤和良性子宫肌瘤的鉴别生物标志物。此外，我们还研究了 GDF-15 是否在子宫肉瘤和良性附件肿瘤、卵巢或子宫内膜癌以及卵巢交界性肿瘤之间存在差异。
分析了 19 名诊断为子宫肉瘤的女性的术前血样中的 GDF-15 含量，并通过免疫分析法进行了分析，并与 50 名接受子宫肌瘤手术的患者的样本以及 20 名绝经前和 20 名绝经后对照组的样本进行了比较。我们之前报告的 43 名交界性肿瘤（n=43）、144 名良性肿瘤（n=144）和 125 名恶性卵巢肿瘤（n=125）以及 510 名子宫内膜癌（n=510）女性的术前 GDF-15 浓度也用于比较。
与子宫肌瘤组（647ng/L）、绝经前和绝经后对照组（363 和 545ng/L）以及良性卵巢肿瘤组（591ng/L）相比，子宫肉瘤组的循环 GDF-15 浓度中位数升高（所有 P≤0.007），但与卵巢交界性肿瘤（718ng/L）或卵巢（1242ng/L）或子宫内膜癌（1076ng/L）组无显著差异。高 GDF-15 水平与平滑肌肉瘤显著相关（P=0.036）、晚期疾病（国际妇产科联合会分期 III/IV 期，P=0.013）、大肿瘤（≥10cm，P=0.009）和不良预后（P=0.022）。
循环 GDF-15 可能是术前识别恶性盆腔疾病的一种很有前途的新型生物标志物。需要进一步的大型前瞻性研究来评估 GDF-15 作为区分良性子宫肌瘤和侵袭性肉瘤的鉴别标志物以及作为指导手术和系统治疗的标志物的临床应用价值。
