AUTHOR=Liu Zuo , Xiao Zengtuan , Wang Xiaofei , Zhang Lianmin , Zhang Zhenfa 

TITLE=Ion channel gene GJB2 influences the intercellular communication by Up-regulating the SPP1 signaling pathway identified by the single-cell RNA sequencing in lung adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1146976

DOI=10.3389/fonc.2023.1146976

ISSN=2234-943X

ABSTRACT=<sec><title>Objective</title><p>Firstly, observe the prognostic significance and the biological functional effects of gap junction protein beta 2 (<italic>GJB2</italic> or Cx26) in lung adenocarcinoma (LUAD). Subsequently, explore the role played by <italic>GJB2</italic> in intercellular communication by single-cell RNA sequencing.</p></sec><sec><title>Method</title><p>We made a differential analysis of <italic>GJB2</italic> expression through public databases and investigated the clinical characteristics and prognostic significance. ESTIMATE analysis and Tumor Immune Estimation Resource (TIMER) database were utilized to illustrate the association of <italic>GJB2</italic> with immune infiltration and components of the tumor microenvironment. Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Gene set enrichment analysis (GSEA) were performed to study the biological function of <italic>GJB2</italic>. Cell-cell communication was analyzed using the CellChat R package through sc-RNA data.</p></sec><sec><title>Results</title><p><italic>GJB2</italic> has an outstanding prognosis value in LUAD and a close relationship was found between <italic>GJB2</italic> and immune infiltration in LUAD. <italic>GJB2</italic> could participate in several tumor biological processes, including extracellular matrix remodeling and upregulation of multiple cancer-related active pathways. <italic>GJB2</italic> related hub-genes influence intercellular communication through the SPP1 signaling pathway.</p></sec><sec><title>Conclusion</title><p>Our study illustrates one mechanism by which <italic>GJB2</italic> exerts its cancer-specific relevant effects, that is, causing changes in intercellular communication through the SPP1 signaling pathway. Blockade of this pathway may limit the functional role of <italic>GJB2</italic> and provide us with promising new perceptions for LUAD treatment.</p></sec>