Exosomal ZFPL1 Identifies Neuroendocrine and Stem Cell-Like Prostate Cancer Subtypes?

BACKGROUND

Calcitonin (CT) and its receptor promote prostate cancer (PC) progression and metastasis. Identifying downstream CT-regulated genes may provide clinically useful biomarkers.

METHODS

Subtraction hybridization was used to identify CT-inducible genes. Expression of zinc finger protein-like 1 (ZFPL1) was examined in malignant versus benign prostate tissues and evaluated for regulation by CT and androgens. Exosomal secretion of ZFPL1 protein was assessed, and plasma levels were measured in PC patients compared with cancer-free individuals. Immunohistochemistry was performed to assess ZFPL1 localization with neuroendocrine (NE) and stem cell markers.

RESULTS

ZFPL1 was strongly expressed in malignant prostates but nearly absent in benign tissues. Its expression was upregulated by both CT and androgens. ZFPL1 protein was secreted through exosomes, and plasma concentrations in PC patients were at least fourfold higher than in cancer-free controls. Immunohistochemistry confirmed ZFPL1 co-localization with NE and stem cell markers, suggesting an association with aggressive, androgen-resistant PC.

CONCLUSIONS

ZFPL1 is a CT- and androgen-regulated protein selectively expressed in malignant prostate cells and secreted via exosomes. Its elevated plasma levels and association with aggressive disease highlight its promise as a non-invasive biomarker for PC detection and monitoring.