Screening and validation of plasma long non-coding RNAs as biomarkers for the early diagnosis and staging of oral squamous cell carcinoma.

Abstract

Oral squamous cell carcinoma (OSCC), characterized by a high recurrence rate, a poor prognosis and high morbidity, is the most prevalent malignancy of the oral cavity. The aberrant expression of long non-coding RNAs (lncRNAs) may lead to the development of various diseases, including cancer. Delayed diagnosis is the main reason for the poor prognosis. Therefore, the present study aimed to investigate the differential expression profiles of plasma lncRNAs in OSCC in order to screen target lncRNAs as biomarkers for the early diagnosis and staging of OSCC. The expression profiles of lncRNAs and mRNAs in OSCC were analyzed by microarray analysis. A total of 14 candidate lncRNAs were selected and analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the array homologous samples. Subsequently, 4 target lncRNAs were measured by RT-qPCR in a large cohort, including 28 cases with TNM I/II [early-stage squamous cell carcinoma (ESCC) group], 36 cases with TNM III/IV [advanced-stage squamous cell carcinoma (ASCC) group], 16 cases with dysplasia [oral premalignant lesion (OPL) group] and 16 healthy controls (H group). Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate the diagnostic effects of the combined lncRNAs. In total, 6,606 differentially expressed lncRNAs and 4,196 mRNAs were identified in OSCC. The expression trend of the 14 candidate lncRNAs was consistent with the microarray data. The expression level of ENST00000412740, NR_131012, ENST00000588803 and NR_038323 exhibited significant differences in the H, OPL, ESCC and ASCC groups (P<0.05). ROC curve and logistic regression analyses revealed that the diagnostic efficacy of the combined lncRNAs was more prominent than that of a single lncRNA, particularly in the ESCC and ASCC groups. In conclusion, the present study identified the differential expression profiles of plasma lncRNAs in OSCC and demonstrated that ENST00000412740, NR_131012, ENST00000588803 and NR_038323 may be promising biomarkers for the early diagnosis and staging of OSCC. These findings may provide novel targets for the early diagnosis and staging of OSCC, which may provide an objective basis for clinical decision-making.