Proteomic analysis reveals potential biomarker candidates in serous ovarian tumors – a preliminary study

Abstract

Introduction: Ovarian serous cystadenocarcinoma (SCA), a deadly gynecologic cancer, often goes undetected until the late stages. Tissue proteomics unveils disease heterogeneity, enhancing tumor classification and enabling personalized treatments tailored to individual expression profiles. Material and methods: Tissue samples from 46 serous ovarian tumors were quantified using label-free liquid chromatography-tandem mass spectrometry. We identified 80 proteins differentiating SCA from borderline tumors, 277 distinguishing SCA from benign tumors, and 195 between borderline and benign tumors. Ingenuity pathway analysis revealed increased cell proliferation and RNA processing in SCA and borderline tumors compared to benign tumors, with SCA showing greater oxidative phosphorylation than borderline tumors. Results: Our comparative analysis indicates that upregulated (ASS1 – argininosuccinate synthase 1, CAPS, PPA1, BCAT1, MCM4) and downregulated proteins (MUC5B, SLC4A1, tenascin-XB – TNXB, carbonic anhydrase 1, hemoglobin β) may offer a robust panel for distinguishing SCA from benign and borderline ovarian tumors, potentially aiding in early diagnosis and disease monitoring. The cancer-associated proteins pyridoxal dependent decarboxylase domain containing 1 (AUC: 0.83, 95% CI: 0.66–1), GFPT1 (AUC: 0.84, CI: 0.70–0.89), and HYOU1 (AUC: 0.84, CI: 0.70–0.98) significantly differentiated between low-grade (LGSCA) and high-grade serous cystadenocarcinoma (HGSCA). Low-grade SCA showed significantly greater levels of MZB1 (log<inf>2</inf> fold change (FC): –1.951, p-value: 0.0258), CRABP2 (FC: –2.34, p-value: 0.0016), and BCAM (FC: –1.945, p-value: 0.0197) than borderline cancers. Conclusions: Argininosuccinate synthase 1 and TNXB showed potential as markers of disease progression. Elevated ASS1 was observed in borderline, LGSCA, and HGSCA tumors compared to benign tumors, while TNXB levels progressively declined from benign to borderline, LGSCA, and HGSCA tumors. Our study pinpoints critical biomarkers in serous ovarian tumors for HGSCA progression.