唾液 KLK5 和 uPA 是 OLK 和 OLP 恶性转化的潜在生物标志物。

Salivary KLK5 and uPA are potential biomarkers for malignant transformation of OLK and OLP.

出版信息

Cancer Biomark. 2021;31(4):317-328. doi: 10.3233/CBM-203105.

DOI:10.3233/CBM-203105

Abstract

BACKGROUND

Oral squamous cell carcinoma (OSCC) usually originates from oral potentially malignant disorders (OPMD), such as oral leukoplakia (OLK) and oral lichen planus (OLP). Identifying biomarkers for the early diagnosis and evaluation of malignant transformation in OPMD could improve the survival rate of OSCC patients.

OBJECTIVE

The present study aimed to screen for potential salivary biomarkers for evaluating the malignant transformation of OPMD.

METHODS

Salivary proteases from OLK and OSCC patients or healthy donors and proteases in cultural medium from DOK and Cal-27 cells were detected with a human protease array kit. The concentrations of the salivary Kallikrein 5 (KLK5) and urokinase-type plasminogen activator (uPA) proteases were measured by ELISA. Receiver operating characteristics (ROC) to determine the potential value of these proteases in clinical diagnosis were calculated using SPSS software. Immunohistochemistry was used to detect the KLK5 and uPA expression in the oral organizations.

RESULTS

The salivary protease spectrum was different among patients with OLK and OSCC and healthy donors. KLK5 and uPA levels in saliva tended to increase as the disease progressed (healthy < OPMD [OLK and OLP] < OSCC). ROC curves showed the optimum diagnostic cutoffs for KLK5 as a biomarker for OLK, OLP, and OSCC were 5.97, 6.03, and 9.45 pg/mL, respectively, while the cutoffs for uPA were 17.19, 17.26, and 20.96 pg/mL. Their combined analysis showed a higher sensitivity for the differential diagnosis of disease. Furthermore, higher levels of KLK5 and uPA were observed in OSCC tissues than in OLK and OLP.

CONCLUSIONS

Salivary KLK5 and uPA are potential biomarkers for evaluating OLK and OLP malignant transformation and early diagnosis of OSCC.

摘要

背景

口腔鳞状细胞癌（OSCC）通常起源于口腔潜在恶性疾病（OPMD），如口腔白斑（OLK）和口腔扁平苔藓（OLP）。识别用于早期诊断和评估 OPMD 恶性转化的生物标志物可以提高 OSCC 患者的生存率。

目的

本研究旨在筛选用于评估 OPMD 恶性转化的潜在唾液生物标志物。

方法

使用人蛋白酶谱试剂盒检测 OLK 和 OSCC 患者或健康供体的唾液蛋白酶以及 DOK 和 Cal-27 细胞培养基中的蛋白酶。通过 ELISA 测量唾液激肽释放酶 5（KLK5）和尿激酶型纤溶酶原激活物（uPA）蛋白酶的浓度。使用 SPSS 软件计算这些蛋白酶在临床诊断中的潜在价值的接收者操作特征（ROC）曲线。免疫组织化学用于检测口腔组织中 KLK5 和 uPA 的表达。

结果

OLK 和 OSCC 患者与健康供体的唾液蛋白酶谱不同。随着疾病的进展，唾液中 KLK5 和 uPA 的水平趋于升高（健康<OPMD[OLK 和 OLP]<OSCC）。ROC 曲线显示 KLK5 作为 OLK、OLP 和 OSCC 的生物标志物的最佳诊断截止值分别为 5.97、6.03 和 9.45pg/mL，而 uPA 的截止值分别为 17.19、17.26 和 20.96pg/mL。它们的联合分析显示出更高的疾病鉴别诊断敏感性。此外，OSCC 组织中 KLK5 和 uPA 的水平高于 OLK 和 OLP。