Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

Tongxia Wang; Yan Gao; Xi Wang; Junrui Tian; Yuan Li; Bo Yu; Cuiyu Huang; Hui Li; Huamao Liang; David M Irwin; Huanran Tan; Hongyan Guo

doi:10.21147/j.issn.1000-9604.2022.02.04

Establishment of an optimized CTC detection model consisting of EpCAM, MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

Chin J Cancer Res. 2022 Apr 30;34(2):95-108. doi: 10.21147/j.issn.1000-9604.2022.02.04.

Authors

Tongxia Wang¹, Yan Gao¹, Xi Wang², Junrui Tian², Yuan Li¹, Bo Yu¹, Cuiyu Huang¹, Hui Li², Huamao Liang¹, David M Irwin³, Huanran Tan², Hongyan Guo¹

Affiliations

¹ Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
² Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S1A8, Canada.

PMID: 35685992
PMCID: PMC9086574
DOI: 10.21147/j.issn.1000-9604.2022.02.04

Abstract

Objective: Emerging studies have demonstrated the promising clinical value of circulating tumor cells (CTCs) for diagnosis, disease assessment, treatment monitoring and prognosis in epithelial ovarian cancer. However, the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.

Methods: We enrolled 160 patients with epithelial ovarian cancer as the experimental group, and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group. We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens (EpCAM and MUC1), and used multiple reverse transcription-polymerase chain reaction (RT-PCR) detecting three markers (EpCAM, MUC1 and WT1) for quantification. And then we used a binary logistic regression analysis and focused on EpCAM, MUC1 and WT1 to establish an optimized CTC detection model.

Results: The sensitivity and specificity of the optimized model is 79.4% and 92.2%, respectively. The specificity of the CTC detection model is significantly higher than CA125 (92.2% vs. 82.2%, P=0.044), and the detection rate of CTCs was higher than the positive rate of CA125 (74.5% vs. 58.2%, P=0.069) in early-stage patients (stage I and II). The detection rate of CTCs was significantly higher in patients with ascitic volume ≥500 mL, suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy (P<0.05). The detection rate of CTC^EpCAM ⁺ and CTC^MUC1+ was significantly higher in chemo-resistant patients (26.3% vs. 11.9%; 26.4% vs. 13.4%, P<0.05). The median progression-free survival time for CTC^MUC1+ patients trended to be longer than CTC^MUC1- patients, and overall survival was shorter in CTC^MUC1+ patients (P=0.043).

Conclusions: Our study presents an optimized detection model for CTCs, which consists of the expression levels of three markers (EpCAM, MUC1 and WT1). In comparison with CA125, our model has high specificity and demonstrates better diagnostic values, especially for early-stage ovarian cancer. Detection of CTC^EpCAM+ and CTC^MUC1+ had predictive value for chemotherapy resistance, and the detection of CTC^MUC1+ suggested poor prognosis.

Keywords: Circulating tumor cells; diagnosis and prognosis; epithelial ovarian cancer; optimized detection model.