A Multiplex Biomarker Assay Improves the Prediction of Survival in Epithelial Ovarian Cancer

Abstract

Background/Aim: Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. Materials and Methods: Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. Results: The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05). Conclusion: In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.

Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival

“…Nevertheless, high breast cancer tissue CCL8 mRNA tissue levels have been reported to increase in breast cancers compared to adjacent healthy tissues and to be associated with worse RFS [ 32 , 34 ]. In biliary tract cancers, elevated serum CCL23 predicted a dismal prognosis [ 35 ], and PEA-measured high plasma CCL28 levels implied worse survival in epithelial ovarian cancers [ 36 ]. Again, CCL28 levels in tumor tissue have a favorable prognostic role in luminal breast cancer but are associated with a worse prognosis in TNBC [ 37 ].…”