Circulating Exosomal PCNA: A Biomarker for Early and Pan-Cancer Detection

Detecting multiple cancers with a single, non-invasive liquid biopsy test remains a challenge, as no universally shared cancer biomarker with clinical significance has been identified in bodily fluids. In this study, we identified proliferating cell nuclear antigen (PCNA), a well-established pathological cancer biomarker in tissue biopsies, as being secreted into peripheral bodily fluids within exosomes. Our research demonstrated that cultured cancer cells continuously release large quantities of exosomal PCNA into their surrounding media. Furthermore, we confirmed its presence in human serum. Most importantly, cancer patients exhibited significantly higher levels of exosomal PCNA in their sera compared to healthy individuals. To assess its diagnostic potential, we evaluated the sensitivity and specificity of exosomal PCNA in a cohort of cancer patients and healthy controls. Receiver operating characteristic (ROC) analysis revealed a sensitivity of 77.2% and a specificity of 94.4%. These findings establish exosomal PCNA in peripheral bodily fluids as a promising universal biomarker for the early detection, diagnosis, and monitoring of multiple cancers through liquid biopsy.