SCCA, TSGF, and the Long Non-Coding RNA AC007271.3 are Effective Biomarkers for Diagnosing Oral Squamous Cell Carcinoma.

Background/aims: Oral squamous cell carcinoma (OSCC) is one of the most lethal malignancies worldwide and the most common type of oral cancer, characterized by invasive growth, frequent regional metastases, high recurrence, and poor prognosis. In the current study, we investigated the use of long non-coding RNAs (lncRNAs), tumor-specific growth factor (TSGF), and squamous cell carcinoma antigen (SCCA) as potential biomarkers for OSCC screening.

Methods: LncRNA expression was measured by microarray analysis in three sets of OSCC and paired normal mucosal tissues. The potential lncRNAs involved in OSCC development were investigated by bioinformatics and verification experiments. We also determined the expression of these potential biomarkers in tissue and serum samples in a case-control study of 80 OSCC cases and 70 controls. Receiver operating characteristics, decision curve analysis, and the combined detection of lncRNA AC007271.3, TSGF, and SCCA were carried out to screen for OSCC biomarkers.

Results: A total of 691 lncRNAs (433 upregulated and 258 downregulated) were differentially expressed in OSCC tissues compared with normal controls (p< 0.05). Based on Gene Ontology and pathway analysis, we selected four differentially expressed lncRNAs (AC007271.3, AC007182.6, LOC283481, and RP11-893F2.9), and showed that aberrant AC007271.3 levels in OSCC patients were significantly associated with clinical stage, especially in early-stage disease, in an expanded case-control study. The combination of AC007271.3 and SCCA (AUC=0.902, p< 0.001) showed significantly better ability to discriminate between OSCC and controls compared with SCCA or AC007271.3 alone. Serum AC007271.3, SCCA, and TSGF levels could also discriminate between OSCC and normal controls with sensitivities of 77.6%, 55.0%, and 63.3%, and specificities of 84.5%, 93.3%, and 66.7%, respectively.

Conclusions: These results suggest that AC007271.3, SCCA, and TSGF could be novel circulating biomarkers for the determination of OSCC. However, further validation in large-scale prospective studies is necessary.