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. 2022 Jun 1;22(3):453-459.
doi: 10.17305/bjbms.2021.6404.

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

Renjing Hu  1 , Xiaochun Chen  2 , Shiliang Zhang  3 , Bin Liu  3 , Hao Pei  3 , Fan Tu  3 , Jun Liu  3 , Hao Yu  4
Affiliations

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

Renjing Hu et al. Bosn J Basic Med Sci. .

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.

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Conflict of interest statement

Conflicts of interest: The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart depicting ovarian cancer patient enrollment in the three hospitals.
FIGURE 2
FIGURE 2
Patient exosome characterization (A) TEM images had a clear background and showed that the single exosome diameter was in the range of 100 nm and 200 nm; all the exosomes were clustered and connected. Exosome was encapsulated by holonomic lipid capsule and exhibited double disc-like vesicular structure; (B) Nanoparticle tracking analysis data showed that diameter for some particles was between 0 and 50 nm but their main distributional range was between 50 and 200 nm; the median value of the total particles was approximately 100 nm; (C) Western blotting showed positive expression for CD9, CD63, Tsg101, and Annexin V.
FIGURE 3
FIGURE 3
The levels of plasma exosome-derived fragile site-associated tumor suppressor (FATS) in ovarian cancer (OC) patients and healthy controls (A) The plasma exosome-derived FATS levels in OC patients and healthy controls; the plasma exosome-derived FATS levels in OC patients aged < 60 and >60 years (B), tumor size (C), grade (D), lymph node metastasis state (E), Federation International of Gynecology and Obstetrics stages (F), sides (G), CA-125 levels (H), and status of ascites (I).
FIGURE 4
FIGURE 4
Association of plasma exosome-derived fragile site-associated tumor suppressor levels with 5-DFS and 5-OS in ovarian cancer (OC) patients. Survival curves for plasma exosome-derived FATS levels for prediction of 5-year DFS (A) and 5-year OS (B) in OC patients.
See this image and copyright information in PMC

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