Relevance of STK11 Mutations Regarding Immune Cell Infiltration, Drug Sensitivity, and Cellular Processes in Lung Adenocarcinoma
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Zhenqing Li1,2, Bo Ding1,2, Jianxun Xu1,2
1Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Abstract:
Serine/threonine kinase 11 (STK11) is one member of the serine/threonine kinase family, which is involved in regulating cell polarity, apoptosis, and DNA damage repair. In lung adenocarcinoma (LUAD), it can play as one tumor suppressor and always be mutated. In this study, we aimed to assess the relevance of STK11 mutations in LUAD, in which we also studied the correlation among immune cell infiltration, drug sensitivity, and cellular processes. By performing the bioinformatics analysis of the Cancer Genome Atlas (TCGA) about LUAD patients, we found that the mutation efficiency of STK11 mutations is about 19%. Additionally, the differentially expressed gene analysis showed that there were 746 differentially expressed genes (DEGs) between LUAD patients with and without STK11 mutations. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis showed that the DEGs were enriched in various tumorigenesis signaling pathways and metabolic processes. Among these DEGs, the top ranking 21 genes were found that they were more frequently mutated in the STK11 mutation group than in the wild-type group (p-value<0.01). Finally, the LUAD patients with STK11 mutations suffered the worse immune cell infiltration levels than the LUAD patients with wild-type. The STK11 gene copy number was correlated with immune cell infiltration. Aiming to develop the therapeutic drugs, we performed Genomics of Drug Sensitivity in Cancer (GDSC) data to identify the potential therapeutic candidate and the results showed that Nutlin-3a(-) may be a sensitive drug for LUAD cases harboring STK11 mutations. The specific genes and pathways shown to be associated with LUAD cases involving STK11 mutations may serve as targets for individualized LUAD treatment.
Insights
Serine/threonine kinase 11 (STK11) mutations occur in 19% of lung adenocarcinoma (LUAD) cases, impacting immune infiltration and potentially responding to Nutlin-3a(-). These findings offer targets for personalized LUAD treatment.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Serine/threonine kinase 11 (STK11) is a tumor suppressor involved in cell polarity, apoptosis, and DNA repair.
- STK11 mutations are prevalent in lung adenocarcinoma (LUAD), influencing tumor behavior.
Purpose of the Study:
- To investigate the relevance of STK11 mutations in LUAD.
- To analyze the correlation between STK11 mutations, immune cell infiltration, drug sensitivity, and cellular processes.
Main Methods:
- Bioinformatic analysis of The Cancer Genome Atlas (TCGA) LUAD patient data.
- Differential gene expression analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) enrichment.
- Genomics of Drug Sensitivity in Cancer (GDSC) data analysis for drug sensitivity.
Main Results:
- STK11 mutations were found in approximately 19% of LUAD patients.
- 746 differentially expressed genes (DEGs) were identified, enriched in tumorigenesis and metabolic pathways.
- LUAD patients with STK11 mutations exhibited lower immune cell infiltration, correlated with STK11 gene copy number.
- Nutlin-3a(-) emerged as a potential sensitive drug for LUAD with STK11 mutations.
Conclusions:
- STK11 mutations significantly impact LUAD characteristics, including immune infiltration and cellular processes.
- Identifying specific genes and pathways associated with STK11 mutations can guide individualized LUAD treatment strategies.
- Nutlin-3a(-) shows promise as a targeted therapy for LUAD patients with STK11 mutations.
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