Dataset Information

Bioinformatics analysis to determine the prognostic value and prospective pathway signaling of miR-126 in non-small cell lung cancer.

ABSTRACT:

Background

MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the initiation and development of non-small cell lung cancer (NSCLC). However, further investigation of the specific role of miR-126 in NSCLC is still required.

Methods

An analysis of miR-126 expression in NSCLC was carried out using the Gene Expression Omnibus (GEO) database, and a literature review was also performed. The differentially expressed genes (DEGs) in three mRNA datasets, GSE18842, GSE19804, and GSE101929, from GEO were identified. Following the prediction of hsa-miR-126-5p target genes by TargetScan, the overlap of miR-126 target genes with DEGs in NSCLC was examined. After that, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Finally, an analysis to identify the impact of hub genes on the prognosis of NSCLC was carried out on the basis of a protein-protein interaction (PPI) network constructed using STRING and Cytoscape.

Results

The data in the literature review revealed a trend that miR126 was downregulated in NSCLC. The number of both NSCLC-related and miR-126-related DEGs was 187. Dozens of DEGs were significantly enriched in biological regulation, cell membrane binding, and signal receptor binding. In the PPI network analysis, 3 of 10 identified hub genes, namely NCAPG, MELK, and KIAA0101, were obviously related to poor prognosis in NSCLC; the survival rate was low among patients with high expression levels of these genes. Furthermore, through network analysis, TPX2, HMMR, and ANLN were identified as recessive miR-126-related genes that may be involved in NSCLC.

Conclusions

MiR-126 plays an essential role in the biological processes of NSCLC through binding to target genes and influences the prognosis of patients with the disease.

SUBMITTER: Jiao Z

PROVIDER: S-EPMC7812220 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportancePrevious studies have suggested the importance of the baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level as prognostic markers. The lung immune prognostic index (LIPI) was shown to be associated with progression-free survival (PFS) and overall survival (OS) among patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) but not cytotoxic chemotherapy (CCT).ObjectiveTo determine whether the LIPI is associated with long-term outcomes in pooled analyses of clinical studies of ICI and targeted therapy (TT) for patients with mNSCLC.Design, setting, and participantsAn exploratory pooled analysis was performed of the LIPI on data from 11 randomized clinical multinational trials evaluating ICIs and TT submitted to the US Food and Drug Administration between January 1, 2013, and December 31, 2017, for 4914 patients with mNSCLC. Lung immune prognostic index scores were calculated based on the dNLR and the LDH level per previous publications to generate good, intermediate, and poor composite scores. Multivariable Cox proportional PFS and OS hazard ratios were generated for the dNLR, the LDH level, age, smoking status, histologic characteristics, and Eastern Cooperative Oncology Group performance score.Main outcomes and measuresOverall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores.ResultsEleven mNSCLC randomized trials were analyzed, including 3987 patients with available data. In 5 ICI trials comprising 2440 patients, 1368 patients received ICIs and 1072 patients received CCT. In 6 TT trials comprising 1547 patients, 1110 patients received TT and 437 patients received CCT. A good LIPI score was associated with better OS among patients receiving ICIs (hazard ratio, 0.34; 95% CI, 0.28-0.42), TT (hazard ratio, 0.28; 95% CI, 0.21-0.37), and CCT (hazard ratio, 0.49; 95% CI, 0.40-0.60 in ICI trials; hazard ratio, 0.41; 95% CI, 0.27-0.61 in TT trials) than those with poor LIPI scores. Similar findings were observed in terms of PFS (ICIs: hazard ratio, 0.59; 95% CI, 0.48-0.72; TT: hazard ratio, 0.46; 95% CI, 0.37-0.57; and CCT: hazard ratio, 0.56; 95% CI, 0.45-0.68 in ICI trials; hazard ratio, 0.51; 95% CI, 0.38-0.69 in TT trials).Conclusions and relevanceThe baseline LDH level and dNLR are important prognostic biomarkers irrespective of treatment modality for patients with mNSCLC. As further prospective clinical trial information is collected, the role of the LIPI score can be better defined.