Expression and clinical significance of KLK5-8 in endometrial cancer.

Kallikrein-related peptidase (KLK) family is one of the major serine proteases in tumor microenvironment, which plays a crucial role in cancer invasion and metastasis. A number of KLK family members have been found to be upregulated or downregulated in some cancers, and some KLKs may be potential biomarkers for cancers. However, little is known about the role of KLKs in endometrial carcinoma (EC). In this study, we analyzed the mRNA sequencing data of EC from The Cancer Genome Atlas (TCGA) public database and found that the higher expression of KLK family members 5-8 (KLK5-8) was associated with an aggressive clinicopathologic phenotype and worse prognosis in EC patients. High expression of KLK5-8 was also confirmed in our patients with advanced stage and high-grade EC, as well as in a highly invasive cell line. Our study also demonstrated the differences between the subcellular localization of KLK5-8 and the co-expression of different splicing variants of KLK5-8 in EC cells, suggesting that various isoforms of KLK5-8 may work synergistically to regulate invasion and migration. We found that the elevation of more KLKs in a patient's sample indicated a higher risk of worse survival. Combination of KLK5-8 was shown to be an independent prognostic factor for overall survival by multivariate Cox regression (hazard ratio: 2.215, 95% confidence interval: 1.045-4.694, P=0.038), and may be a promising biomarker.