Several members of the kallikrein-related peptidase family (KLKs) have been reported to represent potential cancer biomarkers for evaluating patient's prognosis. Most previous studies, however, analyzed heterogeneous patient cohorts encompassing different ovarian cancer subtypes (including mucinous, clear cell, low- and high-grade endometroid or serous ovarian cancer). Morphologic, immunohistochemical, molecular biological, and genetic studies clearly divide epithelial ovarian cancer into two broad categories. The high-grade serous and endometroid subtypes belong to the type II carcinomas, which are clinically aggressive neoplasms, whereas all other major subtypes are type I and represent slow growing, indolent neoplasms. High-grade serous ovarian carcinomas account for about 70% of ovarian cancer and display the worst prognosis.
Here, we present the results of the assessment of the mRNA expression levels of KLK6, KLK8-11, and 13-15 in tumor tissue by quantitative PCR in homogeneous patient cohorts including only patients afflicted with advanced high-grade serous ovarian cancer (FIGO stage III/IV).
Pronounced correlations (rs ≈ 0.7) were observed between KLK10/11 and between KLK9/15 mRNA expression, moderate correlations between KLK6/8, KLK6/10, KLK8/10, KLK10/13, and KLK11/13 (rs in all cases ≈ 0.5). These results indicate coordinate expression of some of the analyzed KLKs in this cancer subtype. KLK mRNA levels were not associated with the clinically established parameters residual tumor mass and ascitic fluid volume.
Elevated KLK6 and KLK13 mRNA levels were, on the one hand, linked with shortened overall survival (OS) and/or progression-free survival (PFS), whereas, on the other hand, elevated KLK11, 14, and 15 mRNA levels were associated with prolonged OS and/or PFS. KLK8, 9, and 10 mRNA values were not associated with patients’ outcome.
In conclusion, KLK6, 11, and 13-15 can be considered as prognostic factors in advanced high-grade serous ovarian cancer. Moreover, inhibition of the enzymatic activity of KLK6 and/or KLK13 may represent an attractive approach in ovarian cancer therapy.