Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer.

Ya-Ting Chang,Jau-Song Yu,Wei-Fan Chiang,Shin-Bin Gou,Ian Yi-Feng Chang,Chien-Hua Chen,Lichieh Julie Chu,Tzong-Yuan Wu,Jun-Sheng Wang,Shu-Fang Wu,Sheng-Fu Chiu,Chih-Yen Chien,Kai-Ping Chang,Srinivas Dash,Yen-Chun Liu,Chih-Jou Chen

doi:10.3390/cancers12082273

Abstract

Oral squamous cell carcinoma (OSCC) accounts for >90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.

Highlights

Oral cancer is the sixth-most common cancer worldwide [1,2]
Using the newly developed enzyme-linked immunosorbent assay (ELISA), we examined matrix metalloproteinase-1 (MMP-1) levels in a total of 1160 saliva samples collected from 313 healthy controls (HC), 305 oral potentially malignant disorders (OPMDs) I patients, 273 OPMD II patients, and 269 Oral squamous cell carcinoma (OSCC) patients
Using Youden’s J statistic to select the best cut-off value for comparisons between non-cancerous groups (HC and OPMD) and OSCC, we found that the cut-off value, sensitivity, specificity, and accuracy of pair-A ELISA were 256.5 pg/mL, 76.58%, 86.76%, and 84.40%, respectively (Table 2), whereas the corresponding values for pair-B ELISA were 213.4 pg/mL, 79.93%, 83.5%, and 82.67%

Summary

Introduction

Oral cancer is the sixth-most common cancer worldwide [1,2]. According to World HealthOrganization statistics, more than 657,000 new cases of oral cancer are reported each year [1,3].The incidence rate increases year by year, and the total number of cases is expected to reach 856,000 per year by 2035. Oral cancer is the sixth-most common cancer worldwide [1,2]. Organization statistics, more than 657,000 new cases of oral cancer are reported each year [1,3]. The incidence rate increases year by year, and the total number of cases is expected to reach 856,000 per year by 2035. More than half of these new cases will occur in Asia, and the proportion of cases that end in death is as high as 68% [4]. The average 5-year survival rate for oral cancer patients is about. In Taiwan, oral, oropharyngeal, and hypopharyngeal cancer are the fourth-leading cause of death for all male malignancies, with 7000 newly diagnosed patients and 3000 deaths each year [5]

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Conclusion