A saliva-based surrogate associates with clinical outcome of oral potentially malignant disorders
Ya-Wen Chen1,2, Shine-Gwo Shiah3, Shyng-Shiou Yuan4
1National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan, ROC. ywc@nhri.edu.tw.
Background:
Oral potentially malignant disorders (OPMDs) are precursor lesions with variable risk of progressing to oral squamous cell carcinoma (OSCC). Reliable biomarkers to predict malignant transformation (MT) risk are urgently needed.
Methods:
RNA sequencing and pathway analyses were performed on 18 progressive and 22 non-progressive OPMDs. A prospective, multicenter cohort study (TWOPMD) analysed 1313 saliva samples from eight Taiwan healthcare centers: 356 healthy controls, 860 OPMD patients and 97 OSCC patients. Eight inflammation-related cytokines were quantified using Bio-Plex immunoassay. Cox regression models evaluated 749 OPMD cases with longitudinal follow-up to identify cytokine predictors of malignant transformation.
Results:
Interferon (IFN) signalling was significantly enriched in progressive OPMDs, with IFN signatures correlating strongly with inflammation-related cytokine expression. IL-1β, IL-6, IL-8, TNF-α and IL-10 were significantly dysregulated across the OPMD, OSCC and control groups. Cox regression identified IL-6, IL-6/IL-1Ra ratio, and composite index (IL-6×IL-8)/IL-1Ra as significant MT predictors. Kaplan-Meier analyses confirmed elevated cytokine biomarkers were associated with significantly higher cancer risk (p = 0.02, p = 0.00001, p = 0.002). Incorporation of betel nut chewing status into the cytokine-based models further improved prognostic performance.
Discussion:
Salivary cytokines, particularly IL-6/IL-1Ra ratio, are promising noninvasive biomarkers for predicting oral cancer risk in OPMD patients.
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