3407 - The clinical significance and biological mechanisms of miR-499a in high-tobacco exposed head and neck squamous cell carcinoma

Background

Few studies have directly investigated the differential expression of miRNA between low-tobacco and high-tobacco exposed HNSCC. The purpose of this study is to screen the differentially expressed miRNA and to investigate the clinical significance and potential biological mechanisms in above two groups of HNSCC.

Methods

The HNSCC datasets were obtained from TCGA database. Meanwhile, we collected 22 HNSCC patients in our hospital. The differentially expressed miRNAs between low-tobacco and high-tobacco exposed HNSCC were identified based on log₂FC > 1 and FDR < 0.05. KM survival analysis, Cox regression, chi-square test were used to evaluate the clinical significance of miRNA. The correlation between gene and clinical characteristic was analyzed by WGCNA. TargetScan, miRDB, DIANA databases were used to predict the target genes of miRNA. RT-qPCR was used to identify miRNA expression in HNSCC tissues. p < 0.05 was considered statistically significant.

Results

30 differentially expressed miRNAs were identified between low-tobacco and high-tobacco exposed HNSCC. The patients with high expression of miR-499a had lower overall survival than those with low expression of miR-499a in high-tobacco exposed HNSCC (p = 0.02). Multivariate Cox regression showed that high expression of miR-499a was an independent risk factor for prognosis of high-tobacco exposed HNSCC (HR = 3.26, p = 0.03). Chi-square test showed that miR-499a was related to N stage in high-tobacco exposed HNSCC (p < 0.01). The clinical significance of miR-499a was not found in low-tobacco exposed HNSCC. WGCNA identified genes associated with N stage in high-tobacco exposed HNSCC. The three databases predicted the target genes of miR-499a, which intersected the genes associated with N stage. ZNRF1, AEBP2, NUS1 were obtained. RT-qPCR showed that miR-499a was differentially expressed between low-tobacco and high-tobacco exposed HNSCC in our own patients.

Conclusions

30 differentially expressed miRNAs are identified between low-tobacco and high-tobacco exposed HNSCC. In high-tobacco exposed HNSCC, highly expressed miR-499a may promote lymph node metastasis by down-regulating one or more of ZNRF1, AEBP2, NUS1, resulting in shortened patient survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.