Abstract
MicroRNAs (miRNAs) are small regulatory non-coding RNAs for which altered expression in cancers can serve as potential biomarkers for diseases. We here investigated whether circulating miRNAs can serve as biomarkers for predicting post-operational recurrence of oral squamous cell carcinoma (OSCC) in patients. Plasma samples from 8 Danish OSCC patients were collected before, and one year after surgical operation, as well as from 3 Danish healthy controls and subjected to miRNA profiling by next generation sequencing. Disease recurrence did not occur in the 8 patients when the post-operative plasma samples were collected. Based on the sequencing data, three up-regulated miRNAs (miR-148a-3p, miR-26a-5p and miR-21-5p) and three down-regulated miRNAs (miR-375, miR-92b-3p and miR-486-5p) in the OSCC samples compared to healthy controls were selected for qRT-PCR validation in a Chinese cohort of 20 plasma samples collected before, and 9-12 months after surgical operation, and 18 healthy controls. Disease recurrence had occurred in 8 out of the 20 Chinese patients at the time their post-operative plasma samples were collected. The results of qRT-PCR showed that down-regulation of miR-486-5p, miR-375 and miR-92b-3p were highly associated with OSCC recurrence. This study indicates that the plasma miRNA profile is altered in OSCC during its progression and can be used to monitor the likelihood of OSCC recurrence in patients after surgery.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common human cancers worldwide
Small RNA deep sequencing was performed on a Danish cohort of pre-operative and post-operative plasma collected from 8 oral squamous cell carcinoma (OSCC) patients and 3 healthy controls
MiR-4865p was highly associated with OSCC recurrence 9-12 months after surgery, since expression of miR-486-5p was not significantly increased in post-operative samples compared to the expression in pre-operative samples in patients with OSCC recurrence but the increase was significant in patients without OSCC recurrence
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common human cancers worldwide. MiRNA expression is usually dramatically altered in cancer, and it has been proven that miRNAs can serve as diagnostic and therapeutic biomarkers for various cancers www.impactjournals.com/oncotarget [7, 8]. Both tumor-suppressive and oncogenic miRNAs whose expressions are either down- or up-regulated in cancer have been discovered [9, 10]. Cell-free miRNAs, circulating in body fluids such as plasma, serum, urine and saliva, can serve as minimally invasive diagnostic and prognostic biomarkers for cancers [11]. Generation sequencing (NGS) of such RNAs has been used to identify specific changes in circulating miRNAs in lung-, breastand nasopharyngeal cancer [12,13,14]
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