Title
Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
Date Issued
01 February 2022
Access level
open access
Resource Type
journal article
Author(s)
Blandino A.
Scherer D.
Rounge T.B.
Umu S.U.
Boekstegers F.
Barahona Ponce C.
Marcelain K.
Gárate-Calderón V.
Waldenberger M.
Morales E.
Rojas A.
Munoz C.
Retamales J.
de Toro G.
Barajas O.
Rivera M.T.
Cortés A.
Loader D.
Saavedra J.
Gutiérrez L.
Ortega A.
Bertrán M.E.
Gabler F.
Campos M.
Alvarado J.
Moisán F.
Spencer L.
Nervi B.
Carvajal-Hausdorf D.E.
Losada H.
Almau M.
Fernández P.
Gallegos I.
Olloquequi J.
Fuentes-Guajardo M.
Gonzalez-Jose R.
Bortolini M.C.
Ruiz Linares A.
Rothhammer F.
Bermejo J.L.
Publisher(s)
MDPI
Abstract
Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candi-dates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncR-NAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04–1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.
Volume
14
Issue
3
Language
English
OCDE Knowledge area
Genética humana Oncología
Scopus EID
2-s2.0-85123375413
Source
Cancers
ISSN of the container
20726694
Sponsor(s)
Funding: This study was supported by the European Union’s Horizon 2020 research and innovation program (grant 825741), the German Academic Exchange Service (DAAD) (grant 91778799), the Deutsche Forschungsgemeinschaft (grant LO 1928/11-1, project number 424112940), and the Biobank of the University of Chile (BTUCH). The funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Acknowledgments: The authors gratefully acknowledge the data storage service SDS@hd supported by the Ministry of Science, Research, and the Arts Baden-Württemberg (MWK) and the German Research Foundation (DFG) through grants INST 35/1314-1 FUGG and INST 35/1503-1 FUGG.
Sources of information: Directorio de Producción Científica Scopus