Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis

J Cancer. 2020 Sep 14;11(21):6445-6453. doi: 10.7150/jca.48531. eCollection 2020.

Abstract

The main diagnostic indicators of ovarian cancer (OC), including carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4), show good sensitivity and poor specificity or vice versa. This study investigated changes in CA125 and HE4 expression and their correlation in serum-derived exosomes of 55 patients with OC (OC group), 33 patients with malignant tumors (non-OC group), and 55 normal controls (NC group). We compared serum and exosomal CA125 and HE4 levels to determine whether their contents in exosomes were elevated. We also compared the diagnostic efficacy of serum HE4, serum CA125, exosomal CA125, and serum HE4+exosomal CA125 in OC using the receiver operating characteristic (ROC) curve. CA125 levels in serum-derived exosomes in all groups significantly increased (P < 0.0001) compared with serum CA125 levels. HE4 was undetected in exosomes. The ROC curve showed the following values: serum CA125: 0.9093 (area), 87.27% (sensitivity), and 90.91% (specificity); serum HE4: 0.9302, 83.64%, and 94.55%; exosomal CA125: 0.9755, 94.55%, and 92.73%; and serum HE4+exosomal CA125: 0.9861, 96.36%, and 92.73%. In conclusion, CA125 can be detected at higher levels in exosomes than in serum, significantly improving OC diagnosis sensitivity. The serum HE4+exosomal CA125 combination significantly improves OC diagnostic efficiency.

Keywords: carbohydrate antigen 125; exosome; human epididymis protein 4; ovarian cancer.