Glycodelin A is a prognostic marker to predict poor outcome in advanced stage ovarian cancer patients

Abstract

BackgroundGlycodelin is a cell surface glycoprotein offering a unique gender specific carbohydrate configuration. Sialylated carbohydrate structures, which are unusual for mammals, characterize Glycodelin isolated from amniotic fluid (Glycodelin A, GdA). Glycodelin in general exerts multiple, partly opposing functions ranging from immunosuppression to cell differentiation. As these markedly influence tumorigenesis, this study aimed to clarify whether expression of different Glycodelin isoforms is related to clinicopathological characteristics and prognosis of ovarian cancer patients. Further the use of Glycodelin as a serum marker in benign and malignant ovarian diseases was evaluated.MethodsOvarian cancer specimens (n = 152) were stained for Glycodelin with carbohydrate and peptide specific antibodies. Associations between Glycodelin expression and histological grading, FIGO stage as well as patient’s prognosis were examined. Glycodelin was correlated to expression of gonadotropin receptors and mucin-1, which are discussed as ovarian cancer tissue markers. In addition, Glycodelin serum concentrations were analyzed in patients suffering from benign (n = 73) or malignant (n = 38) ovarian neoplasias.ResultsGlycodelin A was found to be an independent prognostic marker for poor prognosis in advanced ovarian cancer patients. GdA staining correlated with gonadotropin receptor (FSHR and LHCGR) and with hCG expression. Gd expression showed a positive correlation with a tumour-associated epitope of mucin 1 (TA-MUC1). Further, compared to ovarian cancer, serum Gd was increased in patients with benign ovarian tumors.ConclusionGlycodelin A might be related to tumor aggressiveness and poor clinical outcome in advanced epithelial ovarian cancer. Glycodelin serum levels found in patients suffering from benign ovarian tumors, might contribute to a more global attenuation during progression of these precursor lesions.

The Role of Glycodelin in the Regulation of the Immune System in the Context of Developing Pregnancy

“…Other authors have shown that GdA (PAEP) is expressed in the hematopoietic system by erythroid progenitors, but not by mature erythrocytes, platelets, mononuclear phagocytes or lymphocytes [29]. Finally, it is worth noting that GdA expression is observed not only in healthy tissues of the reproductive tract, but also in certain types of cancer: lung, breast, endometrium, ovaries, and melanoma cells [28,57,64,65,82]. It has been shown that GdA can be used as a biomarker to track the progression of a tumor, as has been shown in non-small cell lung cancer, recurrence or metastatic spread [11].…”

THR alpha and its subtypes alpha1 and alpha2 are prognostic markers for survival of ovarian cancer patients

“…In that case it is negatively correlated to the expression of THRa1 in the nucleus (cc = -0.166, p = 0.048) and THRa2 in the nucleus (cc = -0.268, p = 0.001). An immunosuppressive glycoprotein that is connected to TA-MUC1 is glycodelin and its specific glycoform glycodelin A [33,34]. Glycodelin A showed a positive correlation to THRa2 in the cytoplasm (cc = 0.170, p = 0.037).…”

The Roles of Glycodelin in Cancer Development and Progression

“…Glycodelin expression varies with different histopathological subtypes of ovarian cancers, which may involve variant malignant evolution processes. Glycodelin is expressed in epithelial ovarian cancer tissues including serous, mucinous, endometrioid, and clear cell cancer types and non-epithelial granulose cell ovarian cancer ( 18 , 21 , 22 ). Among the above histopathological subtypes, glycodelin expression in serous ovarian carcinoma and GdA in mucinous ovarian carcinoma are the intensest ( 21 , 22 ) (Table 3 ).…”

“…Riittinen et al did not find any significant dissimilarity of glycodelin expression in cysts fluids among benign, borderline and malignant ovarian lesions ( 29 ). Scholz et al revealed glycodelin level in patients’ serum was higher in benign ovarian tumors than in ovarian cancers ( 22 ). Benign or borderline ovarian tumors can be considered as precursor lesions of ovarian cancer and the inflammation of ovarian epithelium can increase the risk of malignant transformation ( 30 , 31 ).…”