Screening of T Cell-Related Long Noncoding RNA-MicroRNA-mRNA Regulatory Networks in Non-Small-Cell Lung Cancer

Abstract EN

Background.

Lung cancer (LC) has the highest mortality rate among all the other types of cancer in the world.

T cells are known to be the key factor in inducing the immune response during LC.

Objective.

In this study, we aimed to screen and analyze RNAs associated with CD8(+) T cells and activated memory CD4(+) T cells in lung adenocarcinomas, a subtype of non-small-cell lung cancer (NSCLC-LUAD).

Methods.

Gene expression RNA-seq data and clinical data of NSCLC-LUAD were downloaded from the XENA database.

The data were divided into low scores and high scores based on the Stromal and Immune scores.

Then, all the genes were screened for identifying those specifically associated with CD8(+) T cells and activated memory CD4(+) T cells.

The screened genes were used for the construction of the protein-protein interaction (PPI) network and for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis along with prognosis analysis.

Based on the results of the prognostic analysis, the prognostic-related genes were used to analyze long noncoding (lnc)RNA-micro(mi)RNA-mRNA networks and to predict small chemical molecules.

Results.

According to the Immune and Stromal scores, a total of 885 upregulated and 29 downregulated RNAs were identified.

A total of 90 differentially expressed genes (DEGs) were found to be related to CD8(+) T immune cells, and 48 DEGs were related to activated memory CD4(+) T cells.

GPR174 and CD226 suggested a favorable prognosis.

For CD8(+) and activated memory CD4(+) T cells, 112 and 113 PPI edges were obtained, respectively.

GPR174 was found to be regulated by hsa-miR-19b-5p and hsa-miR-19b-2-5p, and both of these two miRNAs were regulated by lncRNA PCED1B-AS1.

CD226 was regulated by hsa-miR-379-5p, which was in turn regulated by lncRNA RP11-81H14.2.

Conclusion.

Our findings provide a deeper understanding of the T cell-related ceRNA regulatory mechanism in NSCLC-LUAD pathogenesis.