Potential of osteopontin in the management of epithelial ovarian cancer

Abstract

Background Osteopontin (sOPN) is a promising blood tumour marker for detecting epithelial ovarian cancer (EOC). However, other clinical uses of sOPN as a tumour marker in EOC are still lacking. Since sOPN concentrations in serum are not associated with those in ascites, we compared clinical value of sOPN concentrations in the two body fluids. Patients and methods The study included 31 women with advanced EOC and 34 women with benign gynaecological pathology. In the EOC group, serum for sOPN analysis was obtained preoperatively, after primary debulking surgery and after chemotherapy. In the control group, serum was obtained before and after surgery. Ascites and peritoneal fluid were obtained during surgery. sOPN concentrations were determined by flow cytometry bead-based assay. Results The sensitivity and specificity of sOPN in detecting EOC was 91.2% and 90.3% (cut-off = 47.4 ng/ml) in serum, and 96.8% and 100% (cut-off = 529.5 ng/ml) in ascites. Kaplan-Meier analysis showed a significant association between higher serum sOPN concentration and overall survival (p = 0.018) or progression free survival (p = 0.008). Higher ascites sOPN concentrations were associated with suboptimally debulked tumour and unresectable disease. Higher serum sOPN concentrations were associated with refractory disease or incomplete response to platinum-based chemotherapy. Conclusions The study showed that ascites sOPN level mirrors present disease and is superior to serum level for diagnostic purposes and surgical planning, although the end result of treatment is the response of the whole body in fighting the disease. The preoperative sOPN concentration in serum thus better reflects disease outcome.

Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling

“…Clinically, OPN is a serum biomarker for ovarian cancer detection (11)(12)(13). In addition, elevated OPN in blood and ascites fluid is associated with platinum resistance and poor survival in ovarian cancer (14)(15)(16). OPN signals through CD44 and integrin receptors to activate multiple downstream signaling pathways, including PI3K/AKT, MEK/ERK, and JAK/STAT pathways (17)(18)(19)(20).…”

Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

“…For instance, MAP3K8 and AURKA identified by our phosphoproteomic interpretations are predictive biomarkers for treatment efficacy and mediators of anti-tumor activities in solid cancers 40,41 . Interestingly, we also observe dysregulation of osteopontin-mediated events, which is a key player in creating an immunosuppressive and pro-tumorigenic microenvironment, and is reported as a prognostic marker in a range of solid tumors 18,19 .…”

“…Potential kinase-targeted therapy targets identified in this group include MAP3K8, GRK2, and AURKA. Interestingly, osteopontin-mediated events and associated pathways, previously linked to cancer progression, are depleted in both the matrisome and the metabolic subtypes 18,19 .…”

Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatment

“… 17 The carriers of at least one polymorphic NQO1 allele (CT and TT genotypes) had an increased risk of MM compared to those with CC genotype. 19 A recent study showed also the association of FTO variability with MM susceptibility. 20 On the other hand, MMP2 polymorphism was suggested to have a protective role in MM.…”

“…Several studies have shown that polymorphisms in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in aetiology and pathogenesis of MM. 17 , 18 , 19 The most commonly studied GSTM1 null polymorphism showed an increased risk for MM. 17 Similarly, two variant alleles of XRCC1 and XRCC3 were associated with increased risk for MM.…”