IncRNAs与口腔鳞状细胞癌及癌前病变因果关联的孟德尔随机化研究

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【中图分类号】R739.85 【文献标识码】A

Mendelian randomization study of the causal association between IncRNAs andoralsquamouscell carcinomaandprecancerouslesions

HU Yuanyuan， NIU Yuming

DepartmentofStomatology， Gongli Hospital ofShanghai PudongNewArea，Shanghai 201318，China

Corresponding author： NIU Yuming， Email： niuyuming@yeah.net

【Abstract】 Objective To investigate the potential associations between lncRNAs and the risk of oral squamous cellcarcinoma （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 reliabilityand 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，andFAM182B[OR -0.738 ， 95%CI （0.581， 0.937）] may reduce the risk of oral leukoplakia. However，FDRand 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 IncRNAs in the development of oral precancerous lesions.However，future studies with larger sample sizes，functional validation，and multi-omics integrationare needed to further explore their biological mechanisms and clinical potential.

【Keywords】Mendelian randomization; Long non-coding RNAs; Oral squamous cell carcinoma; Oral leukoplakia; Oral lichen planus

口腔鳞状细胞癌（oralsquamouscellcarcinoma，OSCC）是口腔颌面部最常见的恶性肿瘤之一，主要来源于口腔鳞状上皮的恶性转变[1-2]。（剩余10332字）