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. 2023 Dec 2;15(23):5693.
doi: 10.3390/cancers15235693.

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study

Samuel Rodríguez-Zorrilla  1 , Alejandro I Lorenzo-Pouso  1   2 , Stefano Fais  3 , Maria A Logozzi  3 , Davide Mizzoni  4 , Rossella Di Raimo  4 , Alessandro Giuliani  5 , Abel García-García  1   2 , Alba Pérez-Jardón  1   2 , Karem L Ortega  1   6 , Ángel Martínez-González  7 , Mario Pérez-Sayáns  1   2   8
Affiliations

Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study

Samuel Rodríguez-Zorrilla et al. Cancers (Basel). .

Abstract

Background: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy.

Methods: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse.

Results: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse.

Conclusions: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.

Keywords: NTA; liquid biopsy; mouth neoplasm; plasmatic exosomes; screening test.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Boxplot representing the exosome levels and sizes, both presurgical and postsurgical.
Figure 2
Figure 2
Violin plot displaying NTA distribution and quantification of patients affected by relapse (REL+) and not (REL-) of presurgical plasmatic exosome concentrations (nm) showing density probability with kernel smoothing.
Figure 3
Figure 3
Kaplan–Meier curve for disease-free survival in patients with a lower presurgical plasmatic exosome concentration (particles/mL) who survived longer than those with higher concentrations (p = 0.012).
Figure 4
Figure 4
Receiver operating characteristic (ROC) curves to predict oral squamous cell carcinoma relapse based on log10 levels of plasmatic exosome concentrations: (A) ROC plot with its area under the curve (AUC) for presurgical exosomes (p = 0.012); (B) cut-off plot representing the intersection that allows maximizing the level of sensitivity and specificity of the model used; (C) ROC plot with its AUC for postsurgical exosomes (p = 0.035); (D) cut-off plot representing the sensitivity and specificity of the model; (E) ROC plot with its AUC for the difference of concentrations between pre- and postsurgial exosomes (p = 0.043); (F) cut-off plot representing the sensitivity and specificity of the model.
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