Serum Fortilin is a Viable Biomarker of In Vivo Apoptosis

Abstract

Apoptosis plays a critical role in many diseases including cancer and infectious diseases. The assessment of apoptosis occurring in the human body would allow clinicians to diagnose and treat these conditions. However, there is no sensitive and specific serum biomarker of apoptosis reported. Fortilin is a nuclear‐cytosolic shuttle protein with multifunctional implicated in various cellular functions. Since it is a potent anti‐apoptotic molecule and can be secreted into extracellular space via exosomes, we hypothesized that fortilin could be a viable serum biomarker of apoptosis occurring in vivo. Serum fortilin was quantified using ELISA in pre‐ and post‐treatment sera of patients with solid malignancies who were undergoing chemo‐ or radiation therapy, which trigger apoptosis in cancer tissue. The result showed that serum fortilin level was significantly elevated in patients who received anticancer therapy and more sensitive than cytochrome c, nucleosomal DNA, and fragmented cytokeratin‐18 biomarkers. Strikingly, serum fortilin level was elevated in the mouse model of apoptosis‐induced liver damage where Jo2 anti‐Fas antibody was administered to induce Fas‐mediated hepatocyte apoptosis. Moreover, fortilin was released from apoptosing Jurkat cell before plasma membrane integrity was compromised in a well‐defined Fas‐induced apoptosis. In conclusion, serum fortilin is a viable apoptosis biomarker which is secreted from apoptosing cells into the circulation, reflecting the degree of apoptosis occurring in vivo.