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

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.

The Diagnostic and Prognostic Value of Plasmatic Exosome Count in Cancer Patients and in Patients with Other Pathologies

“…An independent study performed in patients with glioblastoma reported comparable results in displaying higher exosome levels in the plasma of glioblastoma patients [17]. More recently, a longitudinal study performed using the NTA in patients with oral cancers has shown that high plasmatic levels of exosomes may be predictive of a recurrence after surgical treatment [18], supporting a previous investigation which revealed different exosome counts before and after surgical treatment [19].…”

“…Of course, the other disease conditions need clinical validation at least comparable to what we have to date for tumor patients. This editorial has emphasized a bulk of clinical results supporting the use of a "plasmatic exosome count" as a new valuable tool in the follow-up of tumor patients [7,[17][18][19][20]. The plasmatic exosome count may be implemented by analyzing other components, including: (i) the exosome size (that has been proven to be smaller in tumor patients than in controls) [16,67]; (ii) the expression of known tumor markers [23][24][25] and (iii) the intraluminal pH of circulating exosomes [13].…”

“…Multicenter clinical studies are of course mandatory in order to validate the existing data in higher patient numbers. However, to perform longitudinal studies in patients undergoing either surgical or/and medical treatment is also mandatory [18], with the aim to use the plasmatic exosome count as a new tool in the clinical follow-up of cancer patients. Another important point is to extend the exosome count to other body fluids, with the purpose to limit unnecessary invasive procedures and reduce public health costs.…”

“…Several unexpected but interesting findings propose the simple measurement of exosome plasmatic levels as a key prognostic value [65][66][67]. The data also suggest that the increased exosome blood count is a hallmark of tumor patients as it is a common finding, regardless of tissue specificity [7,[16][17][18][19].…”