Browsing by Author "Moisan, Fabrizio"

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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
    (2022) Blandino, Alice; Scherer, Dominique; Rounge, Trine B.; Umu, Sinan U.; Boekstegers, Felix; Barahona Ponce, Carol; Marcelain, Katherine; Garate-Calderon, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, Cesar; Retamales, Javier; de Toro, Gonzalo; Barajas, Olga; Rivera, Maria Teresa; Cortes, Analia; Loader, Denisse; Saavedra, Javiera; Gutierrez, Lorena; Ortega, Alejandro; Bertran, Maria Enriqueta; Gabler, Fernando; Campos, Monica; Alvarado, Juan; Moisan, Fabrizio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel E.; Losada, Hector; Almau, Mauricio; Fernandez, Plinio; Gallegos, Ivan; Olloquequi, Jordi; Fuentes-Guajardo, Macarena; Gonzalez-Jose, Rolando; Bortolini, Maria Catira; Gallo, Carla; Linares, Andres Ruiz; Rothhammer, Francisco; Lorenzo Bermejo, Justo
    Simple 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.
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    Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study
    (MEXICAN ASSOC HEPATOLOGY, 2012) Gabriel, Mauricio; Moisan, Fabrizio; Vidal, Marcela; Duarte, Ignacio; Jimenez, Macarena; Izquierdo, Guillermo; Dominguez, Pilar; Mendez, Javier; Soza, Alejandro; Benitez, Carlos; Perez, Rosa; Arrese, Marco; Guerra, Juan; Jarufe, Nicolas; Martinez, Jorge
    Introduction. Steatotic livers have been associated with greater risk of allograft dysfunction in liver transplantation. Our aim was to determinate the prevalence of steatosis in grafts from deceased donors in Chile and to assess the utility of a protocol-bench biopsy as an outcome predictor of steatotic grafts in our transplant program. Material and methods. We prospectively performed protocol-bench graft biopsies from March 2004 to January 2009. Biopsies were analyzed and classified by two independent pathologists. Steatosis severity was graded as normal from absent to < 6%; grade 1: 6-33%; grade 2: > 33-66% and grade 3: > 66%. Results. We analyzed 58 liver grafts from deceased donors. Twenty-nine grafts (50%) were steatotic; 9 of them (16%) with grade 3. Donor age (p < 0.001) and BMI over 25 kg/m(2) (p = 0.012) were significantly associated with the presence of steatosis. There were two primary non-functions (PNF); both in a grade 3 steatotic graft. The 3-year overall survival was lower among recipients with macrovesicular steatotic graft (57%) than recipients with microvesicular (85%) or non-steatotic grafts (95%) (p = 0.026). Conclusion. Macrovesicular steatosis was associated with a poor outcome in this series. A protocol bench-biopsy would be useful to identify these grafts.