Abstract

Carboxypeptidase E: A Prognostic Cancer Biomarker in Tumors and Circulating Exosomes

Y. Peng Loh, Chief and Senior Investigator, Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child health and Human Development, National Institutes of Health (NIH)

Carboxypeptidase E (CPE) and/or a splice variant of CPE (CPE-?N) have been reported to be a good prognostic biomarker for hepatocellular carcinoma (HCC), colorectal cancer  and glioblastoma. Microarray data from the Gene Expression Omnibus (GEO) profile database have also indicated significant overexpression of CPE mRNA in many different human cancer types compared to normal tissue. These included metastatic non-endocrine cervical cancer, renal (clear cell) carcinoma, Ewing sarcoma, glioblastoma and various types of astrocytomas and oligodendrogliomas. High expression of CPE mRNA was also found in neuroendocrine tumors, such as pheochromocytoma/paraganglioma, (PHEO/PGL), pulmonary neuroendocrine tumors and insulinomas. Circulating exosomes mirror the parent cell. Exosomes derived from cancer cells contain mRNA and protein that reflects the parent tumor. We have detected CPE mRNA in exosomes in cell culture media from cancer cell lines including liver, breast, prostate and colorectal cancer cell lines. We have also isolated exosomes from serum of PHEO/PGL patients and showed that they contain CPE/CPE-?N mRNA. In a pilot study the levels of CPE/CPE-?N mRNA was determined by qRT-PCR in circulating exosomes of cancer patients. There was a significantly elevated level of CPE/CPE-?N mRNA levels compared to normal controls. Since this biomarker is elevated in many types of cancers, a serum assay using circulating exsomes could be very useful for: 1. routine screening of population > 60 y of age for early diagnosis of cancer. 2. screening high risk patients for early detection of many cancers including patients with liver cirrhosis, smokers, men with positive PSA test, women with solid ovarian cysts, or carry the gene for breast cancer, PHEO/PGL patients with inherited gene mutations for the disease; 3. post-surgery screening of Stage I & II patients for early detection of recurrence; 4. in clinical trials to test the efficacy of the cancer treatment.