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Common Gene and Immune Cell Dynamics Across Oral Carcinogenesis: A Multi‐Stage Transcriptomic Analysis

Year: 2025
Type: article
Abstract: ABSTRACT Background The progressive process from normal oral tissue (ONT) to precancerous lesions (oral dysplasia [OD], leukoplakia–oral precancerous lesion [OPL]) and ultimately to oral squamous cell carcinoma (OSCC) involves dynamic molecular and immunological alterations. Methods Four transcriptomic datasets were analyzed using GEO2R and the R package “IOBR” for differentially expressed genes (DEGs) and immune infiltration profiling. Two‐sample Mendelian randomization (TSMR) was employed to validate the causal effects of immune cells and genes on 11 oral‐related cohorts. Results WDR66 was the only consistently upregulated DEG across all stages (ONT, OD, OPL, OSCC; p < 0.001), with expression levels increasing from premalignant to malignant tissues. Immune infiltration indicates that neutrophils and CD4+ effector memory T cells (Tem) show high correlation with OSCC and OD (these 2 cells were intersection cells in OSCC based on 3 cohorts, high correlation cells in OD based on 1 cohort). TSMR indicated that WDR66: OR M ( Q 1 , Q 3 ) = 0.8513 (0.8453, 0.8759), p , M ( Q 1 , Q 3 ) = 0.0057 (0.0029, 0.0104); CD4+ T cells: OR M ( Q 1 , Q 3 ) = 0.5888 (0.4556, 0.7254), p , M ( Q 1 , Q 3 ) = 0.0000 (0.0000, 0.0002). Conclusions WDR66 emerges with its expression tightly coupled to CD4+ T cell dysfunction in OSCC.
Authors: Zixuan Liao, Xiaofei Li, Qingchen Ma, Cheng Shi, Xuan Wang, Yang Zhang
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4415684014
FWCI:
Cites: 12
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