Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
Journal
Cancers
ISSN
2072-6694
Date Issued
2022
Author(s)
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
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
Justo Lorenzo Bermejo
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Subjects
gallbladder cancer
;
lncrnas
;
eqtls
;
genetic association study
;
molecular phenotypes
;
long untranslated rna
;
adult
;
article
;
cancer risk
;
clinical feature
;
controlled study
;
expression quantitative trait locus
;
female
;
gallbladder cancer
;
gene expression
;
genetic association
;
genetic variability
;
genotype
;
human
;
major clinical study
;
male
;
middle aged
;
risk factor
;
rna sequence
;
validation study