title: Identification of circulating miRNAs profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma.
abstract: Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed.
authors.affiliation: Research Unit, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: L V
authors.initials: LV
authors.lastname: Gayosso-Gómez
authors.affiliation: Research Unit, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Zárraga-Granados
authors.affiliation: Research Unit, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: P
authors.initials: P
authors.lastname: Paredes-Garcia
authors.affiliation: Department of HLA, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Falfán-Valencia
authors.affiliation: Department of Pathology, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: M E
authors.initials: ME
authors.lastname: Vazquez-Manríquez
authors.affiliation: Pneumology-Oncology Service, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: L M
authors.initials: LM
authors.lastname: Martinez-Barrera
authors.affiliation: Pneumology-Oncology Service, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: P
authors.initials: P
authors.lastname: Castillo-Gonzalez
authors.affiliation: Pneumology-Oncology Service, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: U
authors.initials: U
authors.lastname: Rumbo-Nava
authors.affiliation: Department of Clinical Analysis, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Guevara-Gutierrez
authors.affiliation: Department of Nuclear Medicine, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: B
authors.initials: B
authors.lastname: Rivera-Bravo
authors.affiliation: COPD and Smoking Cessation Clinics, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ramirez-Venegas
authors.affiliation: COPD and Smoking Cessation Clinics, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Sansores
authors.affiliation: Research Unit, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: M C
authors.initials: MC
authors.lastname: Negrete-Garcia
authors.affiliation: Research Unit, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
authors.forename: Blanca
authors.initials: B
authors.lastname: Ortiz-Quintero
keywords: circulating miRNAs; differential diagnosis; lung adenocarcinoma; malignant pleural mesothelioma; non-invasive biomarkers