Diagnostic value of circulating lncRNAs HOTAIR, ANRIL, and MEG3 in oral squamous cell carcinoma and their correlation with clinicopathological features

Abstract

Background

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related morbidity and mortality worldwide, largely due to late-stage diagnosis and lack of reliable non-invasive biomarkers. Long non-coding RNAs (lncRNAs) such as HOTAIR, ANRIL, and MEG3 are emerging as potential liquid biopsy biomarkers in solid tumors. Current study evaluates the plasma expression levels of HOTAIR, ANRIL, and MEG3 in OSCC patients and assess their diagnostic potential and correlation with clinicopathological parameters.

Material and methods

In this case-control study, plasma samples were collected from 80 histologically confirmed treatment-naïve OSCC patients and 40 age- and sex-matched healthy controls. Quantitative real-time PCR (qRT-PCR) was performed to analyze lncRNA expression. Statistical analyses were conducted to assess differential expression, clinicopathological associations, and diagnostic performance via ROC curve analysis.

Results

Plasma HOTAIR and ANRIL were significantly upregulated (3.91- and 5.86-fold), while MEG3 was downregulated (0.12-fold) in OSCC compared to controls (p < 0.001 for all). Elevated levels of HOTAIR and ANRIL were associated with poor histological grade, higher T and N stage, LVI, PNI, necrosis, and advanced stage (p = 0001). MEG3 levels decreased progressively with disease stage. Individually, each lncRNA achieved an AUC of 0.99 with high sensitivity and specificity. The three-lncRNA panel (HOTAIR + ANRIL + MEG3) yielded an AUC of 0.95, with 91.25 % sensitivity and 92.50 % specificity. MEG3 showed the best diagnostic performance for early-stage OSCC.

Conclusion

Plasma lncRNAs HOTAIR, ANRIL, and MEG3 show strong potential as non-invasive diagnostic biomarkers for OSCC, correlating with tumor aggressiveness and early disease detection. These findings support further validation in larger multicentric studies.