Salivary MicroRNAs for Early Detection of Head and Neck Squamous Cell Carcinoma: A Case-Control Study in the High Altitude Mestizo Ecuadorian Population.

Carolina Salazar-Ruales,César Paz-Y-Miño,Alejandro Cabrera-Andrade,Andrés López-Cortés,Paola E Leone,Jessica-Viviana Arguello,Patricia Guevara-Ramírez,Jennyfer M García-Cárdenas,Patricio Peralta

doi:10.1155/2018/9792730

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence worldwide. HNSCC is often diagnosed at advanced stages, incurring significant high mortality and morbidity. The use of saliva, as a noninvasive tool for the diagnosis of cancer, has recently increased. Salivary microRNAs (miRNAs) have emerged as a promising molecular tool for early diagnosis of HNSCC. The aim was to identify the differential expression of salivary miRNAs associated with HNSCC in the high altitude mestizo Ecuadorian population. Using PCR Arrays, miR-122-5p, miR-92a-3p, miR-124-3p, miR-205-5p, and miR-146a-5p were found as the most representative ones. Subsequently, miRNAs expression was confirmed in saliva samples from 108 cases and 108 controls. miR-122-5p, miR-92a-3p, miR-124-3p, and miR-146a-5p showed significant statistical difference between cases and controls with areas under the curve (AUC) of 0.73 (p < 0.001), 0.70 (p < 0.001), 0.71 (p = 0.002), and 0.66 (p = 0.008), respectively. miRNAs were also deregulated in between HNSCC localizations. A differentiated expression of miR-122-5p between oral cancer and oropharynx cancer (AUC of 0.96 p = 0.01) was found: miR-124-3p between larynx and pharynx (AUC = 0.97, p < 0.01) and miR-146a-5p between larynx, oropharynx, and oral cavity (AUC = 0.96, p = 0.01). Moreover, miR-122-5p, miR-124-3p, miR-205-5p, and miR-146a-5p could differentiate between HPV+ and HPV- (p=0.004). Finally, the expression profiles of the five miRNAs were evaluated to discriminate HNSCC patient's tumor stages (TNM 2-4). miR-122-5p differentiates TNM 2 and 3 (p = 0.002, AUC = 0.92), miR-124-3p TNM 2, 3, and 4 (p < 0.001, AUC = 98), miR-146a-5p TNM 2 and 3 (p < 0.001, AUC = 0.97), and miR-92a-3p TNM 3 (p < 0.001, AUC = 0.99). Taken together, these findings show that altered expression of miRNAs could be used as biomarkers for HNSCC diagnosis in the high altitude mestizo Ecuadorian population.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence in the world, with 600,000 new cases per year and a mortality rate between 223,000 and 300,000 deaths [1,2,3,4,5]
From the PCR Arrays, miR-122-5p, miR-92a-3p, miR-1243p, miR-205-5p, and miR-146a-5p were selected as the most representative ones in the Ecuadorian HNSCC population based on fold-change >2 (p < 0.05). miR-122-5p and miR146a-5p were upregulated while miR-92a-3p, miR-124-3p, and miR-205-5p were downregulated
The increased incidence of HNSCC patients contrasts with the lack of early diagnosis biomarkers that reduce cancerrelated morbidity and mortality rates [36]. miRNA profiles have been shown as potentially useful biomarkers in cancer diagnosis [36,37,38,39,40]

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with the highest incidence in the world, with 600,000 new cases per year and a mortality rate between 223,000 and 300,000 deaths [1,2,3,4,5]. Serum Epstein Barr Virus- (EBV-) associated antibodies and circulating cell-free EBV DNA testing have been used for nasopharyngeal cancer diagnosis and screening [8]. This type of cancer has a higher incidence in Southern China [4]. In Ecuador, HNSCC is the third most frequent cancer for women and sixth for men, with 1637 new cases per year, being larynx cancer the most common one [10]

Objectives

Methods

Results

Conclusion