Abstract

Carboxypeptidase E: A Cancer Biomarker 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), could serve as a biomarker for predicting recurrence and survival in certain cancers, although lots remains to be studied to check on its validity and reproducibility. Overexpression 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 [1]. Indeed, CPE mRNA overexpression in resected tumors was significantly correlated with poor prognosis in early-stage HCC [2] and cervical [3] cancer. Since tumor cells release 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 elevated in exosomes isolated from cell culture media of liver, prostate, ovarian, glioblastoma and colorectal cancer cell lines with high compared to low metastatic potential. There was no correlation between the size and numbers of secreted exosomes and the metastatic potential of the cancer cells. Our preliminary studies indicate that CPE mRNA is present and elevated in serum-derived exosomes of many of the patients with different types of cancers including cervical, ovarian and breast cancer, compared to normal controls. Thus circulating exosomal CPE mRNA is a potentially useful biomarker for diagnosis of cancer and early detection of recurrence post-surgery, although much more work lies ahead to develop this as a valid test.