KEY TAKEAWAYS
- The study aimed to explore NKX2-1’s involvement in biological processes, aiding in understanding and enhancing LUSC prognosis and treatment.
- NKX2-1 emerges as a promising biomarker for LUSC prognosis and treatment, potentially improving patient outcomes significantly. Further research is crucial for deeper insights.
Huiyue Lin and the team aimed to investigate NKX2-1’s involvement in biological processes, elucidating its role in lung squamous cell carcinoma (LUSC) development to enhance prognosis and treatment.
The study utilized raw RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to conduct bioinformatics analyses, examining NKX2-1 expression levels in both tumor and normal LUSC tissues. Prognostic value was assessed using survival analysis methods, including Kaplan-Meier curve analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and nomogram construction for overall survival (OS) and progression-free survival (PFS) outcomes.
Differential gene expression analysis identified differentially expressed genes (DEGs), with further investigation into biological mechanisms through Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA).
Additionally, correlations were examined between NKX2-1 expression levels and tumor mutation burden (TMB), tumor microenvironment (TME), and immune cell infiltration to elucidate NKX2-1’s role in LUSC development. They also investigated NKX2-1’s impact on drug therapy, and validation of NKX2-1 protein and gene expression levels in LUSC was performed using immunohistochemistry (IHC) datasets, The Gene Expression Omnibus (GEO) database, and qRT-PCR analysis.
The results revealed that NKX2-1 expression levels were notably lower in LUSC than in normal lung tissue, with significant variations noted across gender, stage, and N classification. Survival analysis indicated high NKX2-1 expression was associated with shorter OS and PFS in LUSC. Multivariate Cox regression analysis identified NKX2-1 expression as an independent prognostic factor. A nomogram was constructed to predict LUSC prognosis based on these findings.
Differential gene expression analysis uncovered 51 upregulated and 49 downregulated differentially expressed genes (DEGs) in the high NKX2-1 expression group, with enrichment observed in cell cycle and DNA replication pathways according to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Analysis of the tumor microenvironment (TME) indicated positive associations between NKX2-1 expression and mast cells resting, neutrophils, monocytes, and T cells CD4 memory resting, while negative associations were observed with M1 macrophages.
The TMB showed a negative correlation with NKX2-1 expression. Pharmacotherapy demonstrated heightened sensitivity in the NKX2-1 low-expression group, while no significant differences were observed in immunotherapy response between NKX2-1 low and high-expression groups. Concordance with TCGA data was found in the analysis of The Gene Expression Omnibus (GEO) datasets.
Immunohistochemistry (IHC) analysis confirmed NKX2-1 protein expression in both LUSC and lung adenocarcinoma (LUAD) tumor tissues, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed significantly lower NKX2-1 expression in LUSC compared to LUAD, consistent with co-expression analysis results.
The study concluded that the NKX2-1 emerges as a promising biomarker for diagnosing and treating LUSC. However, further research is warranted to gain deeper insights into its role in LUSC.
No funding was provided.
Source: https://pubmed.ncbi.nlm.nih.gov/38708353/
Lin H, Wang J, Shi Q, et al. (2024). “Significance of NKX2-1 as a biomarker for clinical prognosis, immune infiltration, and drug therapy in lung squamous cell carcinoma.” PeerJ. 2024 May 1;12:e17338. doi: 10.7717/peerj.17338. PMID: 38708353; PMCID: PMC11069361.
