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

Autores de CIPF

• Irene Pérez Díez

  Autor

• Marta Rosa Hidalgo García

  Autor

• Pablo Malmierca Merlo

  Autor

• Zoraida Andreu Martínez

  Autor

• Sergio Romera Giner

  Autor

• 

  Rosa M Farràs Rivera

  Autor

• María De La Iglesia Vayá

  Autor

• 

  Francisco García García

  Autor

Participantes ajenos a CIPF

• Provencio, M
• Romero, A

Grupos de Investigación

• Laboratorio de Señalización Oncogénica

  

  Jefe/a de Grupo

  Rosa M Farràs Rivera

• Unidad de Bioinformática y Bioestadística

  

  Jefe/a de Grupo

  Francisco García García

• Unidad Mixta CIPF-FISABIO de Imagen Biomédica

Abstract

Simple Summary 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.

Keywords

• NSCLC; biomarkers; functional profiling; meta-analysis; sex characteristics