Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL...

Area of Science:

• Genomics and Molecular Biology
• Cancer Research
• Biomarker Discovery

Background:

• Long noncoding RNAs (lncRNAs) are crucial in cellular processes and hold potential for cancer risk prediction.
• Limited research exists on the relationship between individual genetic variations and lncRNA expression.
• Gallbladder cancer (GBC) risk prediction can be improved by identifying reliable biomarkers.

Purpose of the Study:

• To identify circulating lncRNAs associated with gallbladder cancer (GBC) risk.
• To investigate the association between genetic variants and serum lncRNA expression.
• To develop models for predicting serum lncRNA expression based on individual genotypes.

Main Methods:

• Integration of three datasets: lncRNA expression, lncRNA expression with genotype, and genotype only.
• Preselection of lncRNAs based on expression changes across gallstones, dysplasia, and GBC stages.
• Utilized robust linear and logistic regression, and identified cis-lncRNA-eQTLs (expression quantitative trait loci).

Main Results:

• AC084082.3 and LINC00662 showed increased expression, while C22orf34 decreased along the gallstone to GBC progression.
• Two cis-LINC00662-eQTLs (r² = 0.26) and three cis-C22orf34-eQTLs (r² = 0.24) were identified and validated.
• Genotype-based serum expression of LINC00662 was significantly associated with GBC risk (OR = 1.25, p = 0.02).

Conclusions:

• Preselecting lncRNAs using tissue expression data and leveraging cis-lncRNA-eQTLs aids in identifying circulating lncRNAs linked to cancer risk.
• LINC00662 emerges as a potential circulating biomarker for GBC risk prediction.
• This integrated approach provides a robust strategy for discovering noncoding RNA biomarkers for cancer.