KLK6 and KLK7 are potential early detection biomarkers for ovarian cancer

Ovarian cancer (OVC) has the highest mortality rate among other gynecological cancers. The 5-year survival rate in late stage of OVC decreases as low as 15%, suggesting that early detection is key to reducing OVC mortality. However, early detection remains a challenge for OVC due to the silent symptoms, lack of clinical protocols for regular checkups and absence of reliable early detection biomarkers. The purpose of this project is to identify OVC biomarkers for early detection by using a combination of bioinformatics, OVC cell lines for screening and OVC patient samples for validation. Kallikrein family proteases, KLK6 and KLK7, are significantly overexpressed in a majority of the OVC cell lines tested. In addition, KLK6 and KLK7 were significantly overexpressed in early stage I and II and low grade patient samples relative to normal control, suggesting that these two are potential early detection biomarkers for OVC. KLK6 and KLK7 overexpression was predominant in common OVC subtypes serous and papillary serous, indicating that they can be used for almost 65% of OVC cases. Immunohistochemical studies showed that both KLK6 and KLK7 proteins are highly expressed in epithelial compartment of OVC and this signature is maintained throughout the progression of OVC. The levels of KLK6 and KLK7 were highly elevated in stage I and II OVC sera when compared to normal donor control, suggesting that they have excellent value as potential biomarkers for early detection of OVC in respect to population screening. The addition of KLK6 and KLK7 biomarkers could potentially reduce the high “false negative” rates found in currently common ovarian cancer biomarkers such as cancer antigen-125 (Ca-125) and human epididymis protein 4 (HE4).