Mendelian randomization study of the causal association between lncRNAs and oral squamous cell carcinoma and precancerous lesions

HU Yuanyuan; NIU Yuming

doi:10.12173/j.issn.1004-5511.202508133

Abstract：Objective To investigate the potential associations between lncRNAs and the risk of oral squamous cell carcinoma(OSCC)and oral precancerous lesions(oral leukoplakia and oral lichen planus)using a two-sample Mendelian randomization(MR)approach.Methods Expression profiles were analyzed from the Gene Expression Omnibus database(GSE23558 and GSE85195)to identify differentially expressed lncRNAs.Using the eQTLGen Consortium's cis-eQTLs dataset and genome-wide association analysis data for OSCC and oral precancerous lesions,five two-sample MR models,including inverse variance weighting and MR-Egger regression,were used to assess the causal effects of lncRNAs on OSCC and oral precancerous lesions,using single-nucleotide polymorphisms as instrumental variables.Heterogeneity tests,pleiotropy tests,and sensitivity analyses were performed to assess the reliability and stability of the results.False discovery rate(FDR)and Bonferroni correction were applied to adjust the results.Results MR analysis indicated that HCG22[OR=0.999,95％CI(0.999,1.000)]may reduce the risk of OSCC,FAM30A[OR=1.001,95％CI(1.000,1.002)]may increase the risk of OSCC,and FAM182B[OR=0.738,95％CI(0.581,0.937)]may reduce the risk of oral leukoplakia.However,FDR and Bonferroni analysis confirmed that these results may be false positives.Sensitivity analysis revealed no significant heterogeneity or pleiotropy bias,suggesting that the results are robust.Conclusion Current genetic evidence does not support a robust causal relationship between the selected lncRNAs and OSCC or its precancerous lesions.This study provides preliminary genetic insights into the role of lncRNAs in the development of oral precancerous lesions.However,future studies with larger sample sizes,functional validation,and multi-omics integration are needed to further explore their biological mechanisms and clinical potential.