Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Avenue Mariscal Sucre, 170129 Quito, Ecuador.
Ingeniería en Biotecnología, Facultad de Ingeniería y Ciencias Agropecuarias, Universidad de las Américas, Avenue de los Granados, 170125 Quito, Ecuador.
Biomed Res Int. 2018 Nov 21;2018:9792730. doi: 10.1155/2018/9792730. eCollection 2018.
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.
头颈部鳞状细胞癌（HNSCC）是全球发病率最高的第六大常见癌症。HNSCC 通常在晚期诊断，导致高死亡率和发病率。唾液作为癌症诊断的非侵入性工具，最近的使用有所增加。唾液 microRNAs（miRNAs）已成为 HNSCC 早期诊断的有前途的分子工具。目的是确定与厄瓜多尔高地混血人群 HNSCC 相关的唾液 miRNAs 的差异表达。使用 PCR 阵列，发现 miR-122-5p、miR-92a-3p、miR-124-3p、miR-205-5p 和 miR-146a-5p 是最具代表性的 miRNA。随后，在 108 例病例和 108 例对照的唾液样本中证实了 miRNA 的表达。miR-122-5p、miR-92a-3p、miR-124-3p 和 miR-146a-5p 在病例和对照组之间具有显著的统计学差异，曲线下面积（AUC）分别为 0.73（p < 0.001）、0.70（p < 0.001）、0.71（p = 0.002）和 0.66（p = 0.008）。miRNAs 在 HNSCC 定位之间也失调。发现 miR-122-5p 在口腔癌和口咽癌之间的表达存在差异（AUC 为 0.96，p = 0.01）：miR-124-3p 在喉和咽之间（AUC = 0.97，p < 0.01）和 miR-146a-5p 在喉、口咽和口腔之间（AUC = 0.96，p = 0.01）。此外，miR-122-5p、miR-124-3p、miR-205-5p 和 miR-146a-5p 可以区分 HPV+和 HPV-（p=0.004）。最后，评估了五个 miRNA 的表达谱以区分 HNSCC 患者的肿瘤分期（TNM 2-4）。miR-122-5p 区分 TNM 2 和 3（p = 0.002，AUC = 0.92），miR-124-3p 区分 TNM 2、3 和 4（p < 0.001，AUC = 98），miR-146a-5p 区分 TNM 2 和 3（p < 0.001，AUC = 0.97），miR-92a-3p 区分 TNM 3（p < 0.001，AUC = 0.99）。综上所述，这些发现表明，miRNA 的表达改变可作为厄瓜多尔高地混血人群 HNSCC 诊断的生物标志物。
