Abstract

Early detection and easier follow-up of oral squamous cell carcinoma (OSCC) would significantly improve the morbidity and mortality associated with it. With newer technologies, it has become possible to validate cancer biomarkers in saliva with high sensitivity and specificity. There is however a need to further validate these biomarkers in cohorts of different ethnic groups. Our objective was to validate previously evaluated salivary biomarkers in Indian population. The study enrolled 117 patients. These were grouped into subcatergories of 31 early (TNMstage I-II) and 27 late-stage OSCC (TNM stage III-IV), 30 PMOD and 29 post-treatment patients. There were 42 control subjects. We evaluated 3 protein markers, IL-1β, IL-8 and LGALS3BP using ELISA, from unstimulated saliva samples. Statistical analysis was done to calculate p-value, ROC, AUC, sensitivity, and specificity. Protein markers IL-1β and IL-8 were significantly elevated (p < 0.05) in OSCC patients. Though the markers could not discriminate PMOD and post-treatment subjects from controls, they proved to be significantly discriminatory between OSCC and controls. Both these markers were especially strong discriminators of late stage OSCC (stage III-IV). IL-1β had the most statistically significant discriminative power (AUC = 0.9017) in late-stage OSCC followed by IL-8 (AUC = 0.7619). Although LGALS3BP was not found to be significantly elevated in late stage OSCC patients, but it was a significant discriminator of early stage OSCC (stage I-II) with p-value = 0.0008 and AUC = 0.7296. These salivary biomarkers have been discovered and validated in other ethnic groups earlier. Hence, the fact that these markers were discriminatory in Indian population too, strengthens the possibility of using these salivary biomarkers as screening tools in different ethnic cohorts. Such trials would potentiate use of a non-invasive tool, like saliva for diagnosis and follow-up of oral cancer.

Highlights

  • Oral cancer has become a disease of concern worldwide with up-to 400000 new cases per year with almost 130000 deaths annually

  • For the first time multiple salivary biomarkers were evaluated in Indian population, and the results potentiate the ability of IL-1β, IL-8 and LGALS3BP to be used as independent indicators of oral squamous cell carcinoma (OSCC)

  • Among the three protein markers (IL-1β, IL-8, and LGALS3BPBP) investigated, IL-1β and IL-8 were significantly elevated in all stages of OSCC patients, while LGALS3BP was significantly elevated in early stage OSCCs and PMODs

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Summary

Introduction

Oral cancer has become a disease of concern worldwide with up-to 400000 new cases per year with almost 130000 deaths annually. Further studies have potentiated the significance of salivary biomarkers even for OSCC detection. The authors measured the levels of IL-1β, IL-6, IL-8 and osteopontin in whole saliva samples, which were found to be higher in patients with oral cancer than in healthy controls. While studying cytokines in saliva samples, there are chances that cytokine levels may be altered due to other oral diseases. Cheng et al.[12] compared IL-6 levels in oral cancer, oral lichen planus (OLP), and chronic periodontitis (CP) patients. They found that salivary IL‐6 levels were significantly higher in patients with OSCC than in patients with CP, OLP, and healthy controls. Salivary IL‐8 levels too were significantly higher in patients with OSCC than in patients with CP, but only marginally significantly higher than in healthy controls

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