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Identification of circulating lncRNAs associated with gallbladder cancer risk by tissue-based preselection, Cis-eQTL validation, and analysis of association with genotype-based expression

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, b...

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Main Authors: Blandino, Alice (Author) , Scherer, Dominique (Author) , Rounge, Trine B. (Author) , Umu, Sinan U. (Author) , Boekstegers, Felix (Author) , Barahona Ponce, Carol (Author) , Marcelain, Katherine (Author) , Gárate-Calderón, Valentina (Author) , Waldenberger, Melanie (Author) , Morales, Erik (Author) , Rojas, Armando (Author) , Munoz, César (Author) , Retamales, Javier (Author) , de Toro, Gonzalo (Author) , Barajas, Olga (Author) , Rivera, María Teresa (Author) , Cortés, Analía (Author) , Loader, Denisse (Author) , Saavedra, Javiera (Author) , Gutiérrez, Lorena (Author) , Ortega, Alejandro (Author) , Bertrán, Maria Enriqueta (Author) , Gabler, Fernando (Author) , Campos, Mónica (Author) , Alvarado, Juan (Author) , Moisán, Fabrizio (Author) , Spencer, Loreto (Author) , Nervi, Bruno (Author) , Carvajal-Hausdorf, Daniel E. (Author) , Losada, Héctor (Author) , Almau, Mauricio (Author) , Fernández, Plinio (Author) , Gallegos, Ivan (Author) , Olloquequi, Jordi (Author) , Fuentes-Guajardo, Macarena (Author) , Gonzalez-Jose, Rolando (Author) , Bortolini, Maria Cátira (Author) , Gallo, Carla (Author) , Linares, Andres Ruiz (Author) , Rothhammer Engel, Francisco (Author) , Lorenzo Bermejo, Justo (Author)
Format: Article (Journal)
Language:English
Published: 7 January 2022
In: Cancers
Year: 2022, Volume: 14, Issue: 3, Pages: 1-15
ISSN:2072-6694
DOI:10.3390/cancers14030634
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14030634
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/3/634
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Author Notes:Alice Blandino, Dominique Scherer, Trine B. Rounge, Sinan U. Umu, Felix Boekstegers, Carol Barahona Ponce, Katherine Marcelain, Valentina Gárate-Calderón, Melanie Waldenberger, Erik Morales, Armando Rojas, César Munoz, Javier Retamales, Gonzalo de Toro, Olga Barajas, María Teresa Rivera, Analía Cortés, Denisse Loader, Javiera Saavedra, Lorena Gutiérrez, Alejandro Ortega, Maria Enriqueta Bertrán, Fernando Gabler, Mónica Campos, Juan Alvarado, Fabrizio Moisán, Loreto Spencer, Bruno Nervi, Daniel E. Carvajal-Hausdorf, Héctor Losada, Mauricio Almau, Plinio Fernández, Ivan Gallegos, Jordi Olloquequi, Macarena Fuentes-Guajardo, Rolando Gonzalez-Jose, Maria Cátira Bortolini, Carla Gallo, Andres Ruiz Linares, Francisco Rothhammer and Justo Lorenzo Bermejo
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Summary: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 (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.
Item Description:Gesehen am 01.06.2022
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers14030634

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