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Systematic Review

Functional Signatures in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Sex-Based Differences in Transcriptomic Studies

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Bioinformatics and Biostatistics Unit, Principe Felipe Research Center (CIPF), 46012 Valencia, Spain
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Biomedical Imaging Unit FISABIO-CIPF, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana, 46012 Valencia, Spain
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Atos Research Innovation (ARI), 28037 Madrid, Spain
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Department of Oncogenic Signalling, Principe Felipe Research Center (CIPF), 46012 Valencia, Spain
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Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain
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Spanish National Bioinformatics Institute, ELIXIR-Spain (INB, ELIXIR-ES), C/Eduardo Primo Yúfera, 3, 46012 Valencia, Spain
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(1), 143; https://doi.org/10.3390/cancers13010143
Received: 16 November 2020 / Revised: 29 December 2020 / Accepted: 31 December 2020 / Published: 5 January 2021
(This article belongs to the Special Issue Diagnostic and Predictive Biomarkers in Lung Cancer)
Differences in epidemiological and clinical patterns of lung adenocarcinoma have been described between male and female patients. Our study aimed to assess the molecular mechanisms underlying those differences through functional profiling and meta-analysis of lung adenocarcinoma expression datasets. We discovered an overrepresentation of terms related to acute inflammatory responses in female patients, suggesting an increase in certain cell populations, such as T CD8+ cells, and in interleukin production. We also identified purinergic signaling and lipid metabolism as relevant upregulated functional groups in female lung adenocarcinoma samples. Overall, we identified molecular processes and pathways that will aid the understanding of the differential clinical patterns described in lung adenocarcinoma in male and female patients and provide new pathways for the discovery of novel biomarkers and therapeutic targets.
While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic data. We performed a meta-analysis of the functional profiling of nine public datasets that included 1366 samples from Gene Expression Omnibus and The Cancer Genome Atlas databases. Meta-analysis results from data merged, normalized, and corrected for batch effect show an enrichment for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to the immune response, nucleic acid metabolism, and purinergic signaling. We discovered the overrepresentation of terms associated with the immune response, particularly with the acute inflammatory response, and purinergic signaling in female lung adenocarcinoma patients, which could influence reported clinical differences. Further evaluations of the identified differential biological processes and pathways could lead to the discovery of new biomarkers and therapeutic targets. Our findings also emphasize the relevance of sex-specific analyses in biomedicine, which represents a crucial aspect influencing biological variability in disease. View Full-Text
Keywords: NSCLC; biomarkers; functional profiling; meta-analysis; sex characteristics NSCLC; biomarkers; functional profiling; meta-analysis; sex characteristics
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MDPI and ACS Style

Pérez-Díez, I.; Hidalgo, M.R.; Malmierca-Merlo, P.; Andreu, Z.; Romera-Giner, S.; Farràs, R.; de la Iglesia-Vayá, M.; Provencio, M.; Romero, A.; García-García, F. Functional Signatures in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Sex-Based Differences in Transcriptomic Studies. Cancers 2021, 13, 143. https://doi.org/10.3390/cancers13010143

AMA Style

Pérez-Díez I, Hidalgo MR, Malmierca-Merlo P, Andreu Z, Romera-Giner S, Farràs R, de la Iglesia-Vayá M, Provencio M, Romero A, García-García F. Functional Signatures in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Sex-Based Differences in Transcriptomic Studies. Cancers. 2021; 13(1):143. https://doi.org/10.3390/cancers13010143

Chicago/Turabian Style

Pérez-Díez, Irene, Marta R. Hidalgo, Pablo Malmierca-Merlo, Zoraida Andreu, Sergio Romera-Giner, Rosa Farràs, María de la Iglesia-Vayá, Mariano Provencio, Atocha Romero, and Francisco García-García. 2021. "Functional Signatures in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Sex-Based Differences in Transcriptomic Studies" Cancers 13, no. 1: 143. https://doi.org/10.3390/cancers13010143

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