Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma

Abstract

This study aimed to investigate the role of a panel of salivary cytokines as biomarkers for early detection oral squamous cell carcinoma (OSCC), comparing their levels among healthy individuals, patients with oral leukoplakia (OL), and malignant lesions. Cytokine profiling analysis performed in a minimally invasive sample was correlated with clinicopathological variables in our patient cohorts. Unstimulated saliva was obtained from subjects with OSCC at early (n = 33) and advanced (n = 33) disease, OL with homogeneous (n = 33) and proliferative verrucous (n = 33) clinical presentations, and healthy controls (n = 25). Salivary IL-1α, IL-6, IL-8, IP-10, MCP-1, TNF-α, HCC-1, and PF-4 levels were analyzed by a sensitive bead-based multiplex immunoassay. Mean levels of IL-6, IL-8, TNF-α, HCC-1, MCP-1, and PF-4 differed significantly between OSCC, OL, and control saliva (p < 0.05). We found notably higher IL-6 and TNF-α in advanced compared to early OSCC stages. The area under the curve (AUC) for OSCC vs. control was greater than 0.8 for IL-6, IL-8, TNF-α, and HCC-1, and greater than 0.7 for PF-4. The presence of neck metastases (NM) was associated with increased IL-6 and TNF-α levels. Our findings suggest that salivary IL-6, IL-8, TNF-α, HCC-1, and PF-4 may discriminate between OSCC, OL, and healthy controls. IL-6 and TNF-α may indicate OSCC progression, being distinctive in the presence of NM.

Salivary Cytokines as Biomarkers for Oral Squamous Cell Carcinoma: A Systematic Review

“…By contrast, anti-inflammatory cytokines, such as IL-4, IL-10, and IL-13, counterbalance the proliferative potential of the inflammatory ones. Moreover, they are immunosuppressive agents that can enable tumor cells to evade immune surveillance, thus preventing tumor rejection [22,[26][27][28].…”

“…The imbalance between local and systemic cytokine levels, which may promote tumor growth and progression, provides evidence of the relationship between chronic inflammation and oral cancer or potentially malignant diseases [27]. The pro-inflammatory and pro-angiogenic IL-1, IL-6, IL-8, and TNF-α are involved in OSCC development by promoting cell survival and proliferation.…”

“…In seven studies of Group II [27,28,[43][44][45][46][47], the cytokines salivary level increases regularly when moving gradually from well differentiated to poorly differentiated OSCC lesions. The trend is observed for IL-6, IL-8, TNF-α and IL-1RA, demonstrating that they can be associated with disease aggressiveness and severity.…”

“…The trend is observed for IL-6, IL-8, TNF-α and IL-1RA, demonstrating that they can be associated with disease aggressiveness and severity. Patients with early stage OSCC (stage I/II or T1/T2) have higher concentrations of IL-6, IL-8, IL-1β, TNF-α, IFN-γ, MIP-1β, and Growth Regulated Oncogene (GRO) when compared to controls [27,42,48,49], unveiling a potential discriminatory power of the cytokines' level to reveal early phase OSCC development.…”

“…Finally, it is worth noting that, in nearly all studies, salivary IL-6, IL-8, TNF-α levels in OPMD patients, are lower than in OSCC patients and that, for all cytokines, their levels are significantly different with respect to the control population [27,29,32,34,35,41,[43][44][45][46][47][48]50].…”