Combined Transcriptomic and Proteomic Forecast Analyses for Potential Biomarkers of Smoking‐Induced Benign and Malignant Transformation of Vocal Fold Lesions

ABSTRACT Objective Laryngeal dysplasia and Reinke's edema (RE) are common vocal fold lesions associated with smoking. While the former is cancer prone, most cases of the latter do not undergo malignant transformation. Therefore, we proposed identifying biomarkers of smoking‐induced benign‐malignant transformation of vocal fold lesions. Methods Intraoperative vocal fold tissue specimens were collected from 12 smoking patients, including 4 cases of RE, 4 cases of high‐risk dysplasia (HD), and 4 cases of laryngeal carcinoma (CA), and from 4 nonsmoking vocal fold polyps (VFP) patients. RE and HD were set as experimental groups, and CA and VFP were set as positive and negative control groups, respectively (for subsequent expression analysis of hub genes screened). RNA sequencing and DIA‐MS were employed to screen for differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in RE\HD. Venn analysis was used to identify co‐expressed DEGs\DEPs. Functional enrichment analysis was performed to explore DEG\DEP‐related pathways. LASSO regression and SVM‐RFE algorithm were applied to screen for hub genes. The expression levels and prognosis of the hub genes were analyzed based on the TCGA database. The expression levels of the hub genes were further verified using RT‐qPCR. Results A total of 45 co‐expressed DEGs\DEPs were identified in RE\HD, with significant enrichment observed in the HIF‐1 signaling pathway. Three hub genes were identified: TMPRSS11B, SASH1, and TPRG1, which exhibited reduced expression and were associated with poor prognosis in head and neck squamous carcinomas. RT‐qPCR analysis confirmed that the mRNA levels of TMPRSS11B were highly expressed in RE and low in HD compared to VFP. Conclusion This study reveals that TMPRSS11B may be a potential biomarker of smoking‐induced benign‐malignant transformation of the vocal fold lesions, providing a predictive and therapeutic target for early diagnosis and treatment of laryngeal carcinoma.