Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression

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dc.contributor.authorBlandino, Alice
dc.contributor.authorScherer, Dominique
dc.contributor.authorRounge, Trine B.
dc.contributor.authorUmu, Sinan U.
dc.contributor.authorBoekstegers, Felix
dc.contributor.authorBarahona Ponce, Carol
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorGarate-Calderon, Valentina
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorMorales, Erik
dc.contributor.authorRojas, Armando
dc.contributor.authorMunoz, Cesar
dc.contributor.authorRetamales, Javier
dc.contributor.authorde Toro, Gonzalo
dc.contributor.authorBarajas, Olga
dc.contributor.authorRivera, Maria Teresa
dc.contributor.authorCortes, Analia
dc.contributor.authorLoader, Denisse
dc.contributor.authorSaavedra, Javiera
dc.contributor.authorGutierrez, Lorena
dc.contributor.authorOrtega, Alejandro
dc.contributor.authorBertran, Maria Enriqueta
dc.contributor.authorGabler, Fernando
dc.contributor.authorCampos, Monica
dc.contributor.authorAlvarado, Juan
dc.contributor.authorMoisan, Fabrizio
dc.contributor.authorSpencer, Loreto
dc.contributor.authorNervi, Bruno
dc.contributor.authorCarvajal-Hausdorf, Daniel E.
dc.contributor.authorLosada, Hector
dc.contributor.authorAlmau, Mauricio
dc.contributor.authorFernandez, Plinio
dc.contributor.authorGallegos, Ivan
dc.contributor.authorOlloquequi, Jordi
dc.contributor.authorFuentes-Guajardo, Macarena
dc.contributor.authorGonzalez-Jose, Rolando
dc.contributor.authorBortolini, Maria Catira
dc.contributor.authorGallo, Carla
dc.contributor.authorLinares, Andres Ruiz
dc.contributor.authorRothhammer, Francisco
dc.contributor.authorLorenzo Bermejo, Justo
dc.date.accessioned2025-01-20T21:13:09Z
dc.date.available2025-01-20T21:13:09Z
dc.date.issued2022
dc.description.abstractSimple Summary Gallbladder cancer (GBC) is an aggressive disease with poor prognosis that urgently needs risk biomarkers for prevention. Long noncoding RNAs (lncRNAs) have been linked to various types of cancer and have good potential as circulating biomarkers. Prediction of lncRNA expression based on genotype data may contribute to quantify individual GBC risk even without direct lncRNA expression measurement. In this study, we investigate the relationship between GBC risk and genotype-based expression of circulating lncRNAs. Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates 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 lncRNAs (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 (r(2) = 0.26) and three cis-C22orf34-eQTLs (r(2) = 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.
dc.fuente.origenWOS
dc.identifier.doi10.3390/cancers14030634
dc.identifier.eissn2072-6694
dc.identifier.urihttps://doi.org/10.3390/cancers14030634
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93692
dc.identifier.wosidWOS:000754851800001
dc.issue.numero3
dc.language.isoen
dc.revistaCancers
dc.rightsacceso restringido
dc.subjectgallbladder cancer
dc.subjectlncRNAs
dc.subjecteQTLs
dc.subjectgenetic association study
dc.subjectmolecular phenotypes
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIdentification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
dc.typeartículo
dc.volumen14
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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