Reassessing the Role of Tissue Factor Pathway Inhibitor 2 in Neoplastic and Non-Neoplastic Lesions

Abstract

Tissue factor pathway inhibitor 2 (TFPI2) has emerged as a novel serum biomarker for ovarian cancer, gaining insurance coverage in Japan in 2021. Initially characterized as a tumor suppressor gene, TFPI2 exhibits elevated serum levels in patients with ovarian and endometrial cancers compared to healthy individuals, correlating with poor prognostic outcomes. Conventionally, tumor suppressor genes are expected to be downregulated in malignancies; however, clinical observations reveal a paradoxical increase. This review article investigates the role of TFPI2 in both non-malignant and malignant tissues to elucidate the underlying mechanisms of this discrepancy. We aim to raise global awareness among researchers and clinicians regarding the intriguing functions of TFPI2 and to promote its broader clinical application.