Afamin and Apolipoprotein A-IV: Novel Protein Markers for Ovarian Cancer

Abstract

Comparative proteomics identified the vitamin Ebinding plasma protein afamin as a potential novel tumor marker for ovarian cancer. In addition, we observed in a previous small study decreased plasma concentrations of apolipoprotein A-IV (apoA-IV) in preoperative patients with kidney cancer. The aim of this study was therefore to analyze afamin and apoA-IV in a large case-control study to evaluate the diagnostic utility of the two potential novel tumor markers in ovarian cancer patients. We measured plasma concentrations of afamin and apoA-IV by means of a specific sandwich-type ELISA using affinity-purified polyclonal and monoclonal antibodies in 181 ovarian cancer patients of various clinical stages, 399 patients with benign gynecologic diseases, including endometriosis, and 177 controls and compared results with those for the conventional ovarian cancer tumor marker cancer antigen 125 (CA125). Afamin concentrations decreased from a median of 70.7 mg/L (range, 34.6-116.1 mg/L) in healthy controls to 65.2 mg/L (range, 20.2-206.6 mg/L) in patients with benign gynecologic diseases to 56.0 mg/L (range, 4.7-96.0 mg/L) in ovarian cancer patients (P < 0.001 for all pairwise comparisons). Similar results were obtained with apoA-IV concentrations decreasing from 13.0 mg/dL (range, 5.5-34.0 mg/dL) in controls to 11.7 mg/dL (range, 2.0-32.3 mg/dL) in benign conditions to 9.4 mg/dL (range, 0.3-29.5 mg/ dL) in ovarian cancer (all P < 0.001). Receiver operating characteristic analysis for differentiating ovarian cancer patients from healthy controls revealed for a specificity of 90% sensitivity values of 92.4%, 42.4%, and 40.8% for CA125, afamin, and apoA-IV, respectively. Afamin, but not apoA-IV, added independent diagnostic information to CA125 and age for differentiating ovarian cancer from benign and healthy samples; the odds ratio of ovarian cancer was reduced by 44% for each doubling of afamin (P = 0.032). The relatively low sensitivity, however, clearly indicates that afamin and apoA-IV alone are not sufficiently suitable as diagnostic markers for ovarian cancer. Afamin contributes, however, independent diagnostic information to CA125, thus establishing its potential as an adjunct marker

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

“…The authors however reported no difference in serum VDBP protein levels (by ELISA) between the ovarian cancer cases and healthy controls. Finally, plasma APOA4 was previously reported to be lower in samples from cases of malignant versus benign ovarian neoplasms, but did not add independent diagnostic information to CA125 34. Indeed, no combination of the candidate markers reported here was better than CA125 alone at differentiating malignant from benign ovarian neoplasms.…”

Afamin and adropin in patients with alcohol-induced liver cirrhosis

“…Studies in patients with ovarian cancer and stomach cancer have demonstrated significantly reduced levels of afamin [13]. Moreover, the concentration of afamin was found to be significantly decreased in patients with sepsis and pneumonia [14].…”

A proteomic analysis of human follicular fluid: comparison between fertilized oocytes and non-fertilized oocytes in the same patient

“…Vitronectin is a multifunctional adhesive glycoprotein that plays a significant role in a number of physiological processes such as cell adhesion, cell migration, cell invasion, humoral defense mechanisms, modulation of the immune system and regulation of the plasminogen activation system [23]. Apolipoprotein A-IV, a glycoprotein, is a member of the apoA1/C3/A4/A5 gene cluster that is synthesized by the small intestine and involved in lipid and lipoprotein metabolism [9]. Although the precise function of apolipoprotein A-IV is not known, several studies have suggested that it is associated with cardiovascular disease and might be involved in reverse cholesterol transport, which is important for cholesterol homeostasis and steroidogenesis [21].…”

“…However, a limitation of this study is that we are unable to attribute fertilization to oocyte quality only, although we Fig. 2 Spectral counts of heparan sulfate proteoglycan perlecan in the follicular fluids containing fertilized oocytes (fFF) and non-fertilized oocytes (nfFF) in each patient (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) tried to minimize the influence of sperm quality using ICSI. An increased number of samples would enable the use of a proteomics analysis to identify distinctive biomarkers.…”