Journal Article

KLK7 expression in human tumors: a tissue microarray study on 13,447 tumors

Kind, Simon, Clauditz, Till S., Castillo, Carolina Palacios, Bernreuther, Christian, Jacobsen, Frank, Sauter, Guido, Fraune, Christoph, Lebok, Patrick, Gorbokon, Natalia, Lennartz, Maximilian, Büscheck, Franziska, Hube-Magg, Claudia, Burandt, Eike, Viehweger, Florian, Minner, Sarah, Marx, Andreas H., Wilczak, Waldemar, Steurer, Stefan, Reiswich, Viktor, Hinsch, Andrea, Dwertmann Rico, Sebastian, Schlichter, Ria, Hornsteiner, Lisa S., Kluth, Martina, Menz, Anne, Krech, Till, Simon, Ronald

2024

Overview

Background Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells. Methods To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results KLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis ( p  = 0.0005), blood vessel infiltration ( p  = 0.0037), and lymph vessel infiltration ( p  < 0.0001) in colorectal adenocarcinoma, nodal metastasis in hepatocellular carcinoma ( p  = 0.0382), advanced pathological tumor stage in papillary thyroid cancer ( p  = 0.0132), and low grade of malignancy in a cohort of 719 squamous cell carcinomas from 11 different sites of origin ( p  < 0.0001). Conclusions These data provide a comprehensive overview on KLK7 expression in normal and neoplastic human tissues. The prognostic relevance of KLK7 expression and the possible role of KLK7 as a drug target need to be further investigated.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenocarcinoma / Analysis / Antibodies / Antigens / Biomarkers, Tumor - metabolism / Biomedical and Life Sciences / Biomedicine / Breast cancer / Cancer Research / Chymotrypsin / Colorectal carcinoma / Endometrium / Extracellular matrix / Female / Gastrointestinal tract / Health aspects / Health Promotion and Disease Prevention / Hepatocellular carcinoma / Homeostasis / Humans / Immunohistochemistry / Infiltration / Kallikrein / Kallikrein gene / Kallikreins / Kallikreins - metabolism / KLK7 / Liver cancer / Male / Malignancy / Medicine/Public Health / Metastases / Neoplasms - metabolism / Neoplasms - pathology / Neoplastic human tissues / Oncology / Oral cancer / Ovarian cancer / Ovarian carcinoma / Pancreatic cancer / Papillary thyroid cancer / Papillary thyroid carcinoma / Pathology / Prostate cancer / Proteases / Protein arrays / Proteins / Salivary gland / Serine proteinase / Squamous cell carcinoma / Surgical Oncology / Therapeutic targets / Thyroid cancer / Tissue Array Analysis / Tissue microarray / Tumors