Circulating exosomal protein EFEMP1 and SERPINC1 as diagnostic biomarkers for epithelial ovarian cancer

循环外泌体蛋白 EFEMP1 和 SERPINC1 作为上皮性卵巢癌的诊断生物标志物

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Abstract

OBJECTIVES: Caner-derived exosomes, containing diverse nucleic acids and proteins, are being exploited in diagnostic biomarker development. This study aims to screen and identify the altered exosomal proteins between epithelial ovarian cancer (EOC) patient and healthy volunteers, and to evaluate their diagnostic accuracy for EOC. METHODS: Exosomes were separate by ultracentrifugation, and then subjected to TEM, qNano, and western blot for identification. Exosomal EFEMP1 and SERPINC1 were selected by MS/MS analysis, validated by ELISA in a cohort with 163 healthy donors, 183 EOC patients and 30 patients with benign ovarian tumors. RESULTS: MS/MS analyses identified a total of 207 differential exosomal proteins, including the 122 up-regulated and 85 down-regulated. Exosomal EFEMP1 and SERPINC1 were significantly upregulated in EOC patients compared with those in healthy donors as well as in the benign patients, possessing favorable diagnostic efficiency. The area under the curves (AUCs) were 0.8071, 0.8211, respectively. They also exerted rather high early diagnostic efficiency, as well as the potential to distinguish the malignant patients from the benign individuals. Besides, exosomal SERPINC1 was associated with coagulation index and LE-DVT (lower extremity deep venous thrombosis) in EOC patients. CONCLUSIONS: Exosomal EFEMP1 and SERPINC1 are upregulated and serve as the promising diagnostic biomarkers for EOC.

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