Abstract

Carboxypeptidase E: A Biomarker for Detection of Cancer in 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)

Tumor recurrence and metastasis are the major causes of death in cancer patients. Biomarkers that can predict tumor recurrence in cancer patients who are in the early pathology stage and able to receive curative resection will greatly improve survival. To facilitate early cancer diagnosis and as a companion diagnostic to follow the efficacy of the therapy, such biomarkers should be detected not only in resected tumors, but also in serum to provide a non-invasive assay. Accumulating evidence suggest that carboxypeptidase E (CPE), along with its N-terminal truncated derivative, could serve as a powerful prognostic biomarker for predicting recurrence and survival. Over-expression of carboxypeptidase E (CPE) mRNA is common in many different human cancer types including metastatic cervical cancer, renal (clear cell) carcinoma, Ewing sarcoma, glioblastoma and various types of astrocytomas and oligodendrogliomas. Indeed, CPE mRNA over-expression in resected tumors was significantly correlated with poor prognosis in early-stage HCC and cervical cancer. Since tumor cells release excessive amount of exosomes, which contain mRNAs and proteins that mirror their parent tumor cells, and are readily accessible in nearly all biological fluids, we have developed a method to measure CPE mRNA in exosomes. CPE mRNA was detected in exosomes in cell culture media from liver, prostate, ovarian, glioblastoma and colorectal cancer cell lines. Exosomes from highly metastatic cell lines showed significantly higher copy numbers of CPE mRNA than the low metastatic cell lines from each of these cancer cell lines. In a pilot study, we have measured the levels of CPE mRNA in circulating exosomes of cancer patients and normal healthy controls. Eighty % of patients with various types of cancers including breast, prostate, ovarian, colon and cervical cancer had CPE mRNA copy numbers above the average copy number found in the normal controls. Our preliminary results indicate that CPE mRNA is present a