Salivary transcriptomic profile reveals biomarker candidates for early detection of occlusal dysesthesia: a case–control study

Abstract Background Occlusal dysesthesia (OD) is a rare and highly intractable condition, with no established objective indicators for early detection. This study aimed to analyze the salivary transcriptomic profiles of OD patients and healthy controls to explore potential biomarkers for early OD detection. Methods Saliva samples were collected from 11 OD patients and 11 age- and gender-matched healthy controls, then processed for RNA sequencing. Differential gene expression and functional enrichment analyses were performed. Selected candidate mRNA markers were validated using real-time polymerase chain reaction (PCR). Firth’s penalized logistic regression was applied to assess the association between OD and each candidate mRNA marker. The diagnostic utility of these genes was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Results The total number of identified mRNAs in saliva was 5353 ± 2214 in OD patients and 5075 ± 1482 in controls. A total of 595 significantly differentially expressed mRNAs were identified, including 320 up-regulated and 275 down-regulated. Based on the differential expression profile, 16 mRNAs were selected as potential biomarker candidates, of which 15 were confirmed by real-time PCR. Regression analysis revealed that OSTC , HES1 , HINT2 , VTI1B , SNX6 , and PGRMC1 were associated with increased OD risk, whereas AZGP1 , CLDN3 , SLC27A4 , RRAS , GAS1 , TAGLN , CTTNBP2NL , and PLAC9 were associated with reduced risk. Regarding diagnostic performance, the top three single-gene predictors for OD detection were CLDN3 , RRAS and PGRMC1 (corrected AUC > 0.90), and the top three two-gene panels were CLDN3 + SNX6 , CLDN3 + PGRMC1 , and AZGP1 + SNX6 (corrected AUC > 0.98). Adding a third gene did not improve diagnostic performance compared with the two-gene panels. Conclusion This study provides the first characterization of the salivary transcriptomic profile in OD patients, and identifies potential salivary mRNA biomarker candidates associated with OD. Trial registration Chinese Clinical Trial Registry, ChiCTR2000040994; Registered on 16 December 2020.