Validation of tissue factor pathway inhibitor 2 as a specific biomarker for preoperative prediction of clear cell carcinoma of the ovary

Etsuko Miyagi,Takeharu Yamanaka,Tae Mogami,Satoshi Yamaguchi,Yuka Kasamatsu,Hisamori Kato,Hiroshi Kobayashi,Noriaki Arakawa,Yuki Yamada,Naho Ruiz Yokota,Shoji Nagao,Kentaro Sakamaki,Yasuyuki Hirashima,Yohei Miyagi

doi:10.1007/s10147-021-01914-y

Abstract

BackgroundTissue factor pathway inhibitor 2 (TFPI2) is a novel serum biomarker that discriminates ovarian clear cell carcinoma (CCC) from borderline ovarian tumors (BOTs) and non-clear cell epithelial ovarian cancers (EOCs). Here, we examined the performance of TFPI2 for preoperative diagnosis of CCC.MethodsSerum samples were obtained preoperatively from patients with ovarian masses, who needed surgical treatment at five hospitals in Japan. The diagnostic powers of TFPI2 and cancer antigen 125 (CA125) serum levels to discriminate CCC from BOTs, other EOCs, and benign lesions were compared.ResultsA total of 351 patients including 69 CCCs were analyzed. Serum TFPI2 levels were significantly higher in CCC patients (mean ± SD, 508.2 ± 812.0 pg/mL) than in patients with benign lesions (154.7 ± 46.5), BOTs (181 ± 95.5) and other EOCs (265.4 ± 289.1). TFPI2 had a high diagnostic specificity for CCC (79.5%). In patients with benign ovarian endometriosis, no patient was positive for TFPI2, but 71.4% (15/21) were CA125 positive. TFPI2 showed good performance in discriminating stage II–IV CCC from BOTs and other EOCs (AUC 0.815 for TFPI2 versus 0.505 for CA125) or endometriosis (AUC 0.957 for TFPI2 versus 0.748 for CA125). The diagnostic sensitivity of TFPI2 to discriminate CCC from BOTs and other EOCs was improved from 43.5 to 71.0% when combined with CA125.ConclusionsHigh specificity of TFPI2 for preoperative detection of CCC was verified with the defined cutoff level of TFPI2 in clinical practice. TFPI2 and CA125 may contribute substantially to precise prediction of intractable CCC.

Highlights

Patients and methodsOvarian cancer is currently one of the most lethal gynecological malignancies and the eighth most common cancer in women worldwide
To identify specific serum biomarkers of cell carcinoma (CCC), we focused on a serine protease inhibitor, tissue factor pathway inhibitor 2 (TFPI2; known as placental protein 5) [11], as a candidate specific serum biomarker. [12, 13] A modified proteomics technique, “secretome,” was used to identify Tissue factor pathway inhibitor 2 (TFPI2) in media conditioned by CCC-derived cell lines [13]
Among the 351 eligible serum samples included in this study, 77 were benign ovarian lesions, 65 were borderline ovarian tumors (BOTs), and 209 were epithelial ovarian cancers (EOCs), which included 69 CCC cases

Summary

Introduction

Patients and methodsOvarian cancer is currently one of the most lethal gynecological malignancies and the eighth most common cancer in women worldwide. CCC patients often show low or normal levels of serum cancer CA125 that has the highest sensitivity to detect high grade serous carcinoma [8, 9].

Results

Conclusion