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

Valentina Dikova,Eloisa Jantus-Lewintre,Jose Bagan

doi:10.3390/jcm10081658

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.

Highlights

Oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasia of the oral cavity that accounts for more than 90% of all head and neck (HNC) cancers [1]
We found that patients with homogeneous leukoplakia (HL) and proliferative verrucous leukoplakia (PVL) have significantly higher salivary IL-6, IL-8, Monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factors (TNFs)-α, and HCC-1 than their healthy counterparts (Table 2)
Further comparisons revealed notable elevations of IL-6, IL-8, TNF-α, HCC-1, and Platelet factor 4 (PF-4) levels in OSCC collated to oral leukoplakia (OL) sample cohorts (Figure 1), with increases traceable from early oral cancer stages (Table 2)

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasia of the oral cavity that accounts for more than 90% of all head and neck (HNC) cancers [1]. Oral leukoplakia (OL) is the most common representative, considered to have the highest risk of malignant transformation reaching up to 17% [3,4] The latter exhibits different subtypes out of which the non-homogeneous proliferative verrucous leukoplakia (PVL) presents a higher tendency for cancerous conversion than the homogeneous clinical form according to follow-up studies [5,6]. No study has analyzed differences in salivary cytokines between early and advanced OSCC stages, comparing the results with two OL subgroups as potential pre-cancer disorders: one with the lowest risk, being homogeneous leukoplakia (HL), and one with the highest risk of malignant transformation, being PVL. We intended to study if any of the target biomarkers could indicate the group of cases with neck metastasis within the cancer patients

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Discussion

Conclusion