Extracellular Vesicle - MDM2 -DNA as a Potential Liquid Biopsy Biomarker for Disease Identification in Retroperitoneal Liposarcoma

Objective: We aimed to assess the levels of MDM2-DNA within extracellular vesicles (EVs) isolated from the serum of retroperitoneal liposarcoma (RLS) patients versus healthy donors, as well as within the same patients at the time of surgery versus postoperative surveillance visits. To determine whether EV-MDM2 may serve as a possible first-ever biomarker of liposarcoma recurrence. Background: A hallmark of well-differentiated and dedifferentiated (WD/DD) retroperitoneal liposarcoma is elevated MDM2 due to genome amplification, with recurrence rates of >50% even after complete resection. Imaging technologies frequently cannot resolve recurrent WD/DD-RLS versus postoperative scarring. Early detection of recurrent lesions, for which biomarkers are lacking, would guide surveillance and treatment decisions. Methods: WD/DD-RLS serum samples were collected both at the time of surgery and during follow-up visits from 42 patients, along with sera from healthy donors (n=14). EVs were isolated, DNA purified, and MDM2-DNA levels determined through q-PCR analysis. Nonparametric tests were employed to compare EV-MDM2 DNA levels from patients versus the control group, as well as the time of surgery versus postsurgery conditions. Results: EV-MDM2 levels were significantly higher in WD/DDRLS than controls (P=0.00085). Moreover, EV-MDM2 levels were remarkably decreased in WD/DD-RLS patients after resection (P= 0.00036), reaching values comparable to control group (P= 0.124). During postoperative surveillance, significant increases of EV-MDM2 were observed in some patients, correlating with computed tomography scan evidence of recurrent or persistent postresection disease. Conclusions: Serum EV-MDM2 may serve as a potential biomarker of early recurrent or postoperatively persistent WD/DD-RLS, a disease currently lacking such determinants.