Plasma exosome-derived fragile site-associated tumor suppressor as a powerful prognostic predictor for patients with ovarian cancer.

Renjing Ju,Hao Yu,Xiaochun Chen,Shiliang Zhang,Hao Pei,Bin Liu,Jun Liu,Fan Tu

doi:10.17305/bjbms.2021.6404

Abstract

The objective of the study was to investigate the levels of plasma exosome-derived fragile site-associated tumor suppressor (FATS) and evaluate its prognostic predictive ability in ovarian cancer (OC) patients. Exosome-rich fractions were isolated from the plasma of 90 patients with OC enrolled in this study. The levels of plasma exosome-derived FATS were detected by ELISA. The levels of exosome-derived FATS in OC patients were significantly lower as compared to the healthy controls (P < 0.001). The levels of plasma exosome-derived FATS were higher in OC patients with low grade (1/2), and Federation International of Gynecology and Obstetrics (FIGO) Stages I/II than those in high grade (3/4) and Stages III/IV of the disease (p = 0.003; p < 0.001), respectively. The levels of plasma exosome-derived FATS were significantly higher in OC patients with no lymph node metastasis or no ascites as compared to those with lymph node metastasis or ascites, respectively (both p < 0.001). The levels of plasma exosome-derived FATS were higher in OC patients having CA-125 below 35 U/ml as compared to those with CA-125 greater than 35 U/ml (p < 0.001). Among all enrolled OC patients, both 5-DFS and 5-OS were shorter in patients with lower plasma exosome-derived FATS levels than those with higher levels (both p < 0.001). The area under the receiver operating characteristic curve of plasma exosome-derived FATS was 0.85 (95% CI: 0.76-0.91) for 5-DFS and 0.91 (95% CI: 0.83-0.96) for 5-OS prediction in patients with OC. Plasma exosome-derived FATS levels in OC patients were significantly downregulated. Low levels of plasma exosome-derived FATS had a significant relationship with FIGO Stages III/IV, high grade, ascites, higher levels of CA-125, lymph node metastasis, and prognosis of OC patients. Thus, our findings may provide insights for the development of a new strategy OC treatment.

Highlights

Ovarian cancer (OC) is a gynecological malignancy in the female reproductive system with the highest fatality rate [1, 2]
Low levels of plasma exosome-derived fragile-site associated tumor suppressor (FATS) had a significant relationship with Federation International of Gynecology and Obstetrics (FIGO) stages III/ IV, high grade, ascites, higher levels of CA-125, lymph node metastasis, and prognosis of ovarian cancer (OC) patients
We evaluated the levels of plasma exosome-derived FATS in OC patients at different stages of the disease

Summary

Introduction

Ovarian cancer (OC) is a gynecological malignancy in the female reproductive system with the highest fatality rate [1, 2]. Oncology research includes the discovery of novel tumor suppressor genes and investigations of their roles in the development of tumors [7]. Common fragile sites (CFS) are site-specific unstable regions in the normal genome and include the rare fragile sites [8]. While the role of rare fragile sites in tumors remains unclear, CFS is consistent for many tumor genome mutations, and they are closely related to the occurrence and development of tumors [9]. The introns and expression regulatory regions of fragile-site associated tumor suppressor (FATS) gene are rich in AT repeat sequences and have characteristics of typical fragile locus genes [10]. Due to the heterozygous loss in many genes at this locus, FATS may be closely related to the occurrence of human tumors [11]. After co-transfection of the FATS expression vector, both in vitro and in vivo anti-tumor activities have been reported [12,13]

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Conclusion