The prognostic and diagnostic potential of kallikrein-related peptidases in ovarian cancer

ABSTRACT

Introduction: Ovarian cancer is one of the deadliest malignancies among women worldwide. The lack of early diagnostic markers fuels an unfavorable prognosis as most patients are at an advanced stage when the disease is diagnosed for the first time. The role of the kallikrein-related peptidase (KLK) family in ovarian cancer progression and prognosis has been thoroughly investigated in various studies. Most of these peptidases are upregulated in ovarian cancer tissue compared to normal ovarian tissue and their expression is linked to overall and progression-free survival (OS/PFS). In this review, we address the clinical relevance of KLKs in ovarian cancer and their diagnostic potential.

Areas covered: This review covers the expression and regulation of KLKs in ovarian cancer with focus on the prognostic and diagnostic potential, especially in liquid biopsies.

Expert opinion: In ovarian cancer, several kallikrein-related peptidases are markedly expressed in a tissue-specific manner. Tumor-derived protease secretion results in elevated levels in serum and ascites. KLKs may thus serve as potential biomarkers alone or in combination with other serum tumor markers, such as Cancer Antigen 125 (CA125), for early detection and assessment of the prognosis of ovarian cancer patients.

KEYWORDS:

• Ovarian cancer
• kallikrein-related peptidases
• diagnosis
• serum
• klk

Article highlights

• Tumor-derived kallikrein-related peptidases (KLKs) are prognostic biomarkers and potential targets for therapy in ovarian cancer.

• Since they are secreted proteins, tumor-derived KLKs are also detectable in serum and ascites.

• The evaluation of KLK levels helps to differentiate between malignant and normal/benign ovarian tissue.

• Determination of serum KLKs or a combination thereof, together with other tumor markers, may improve early diagnosis of ovarian cancer. Further clinical studies are needed to validate current findings.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The work was supported in part by a grant from the Wilhelm Sander-Stiftung (2019.085.1), the Deutsche Forschungsgemeinschaft (BR 4733/3-1, BR 4733/4-1, and MA 1236/10-1, respectively), as well as the Kapitel Klinische Forschung (Klinikum Rechts der Isar, TUM).