Differences in genetics and microenvironment of lung adenocarcinoma patients with or without TP53 mutation
| Autor: | Cheng Zhan, Zhencong Chen, Besskaya Valeria, Qun Wang, Zongwu Lin, Miao Lin, Guangyao Shan, Dejun Zeng, Zhengyang Hu, Yanjun Yi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Lung adenocarcinoma Lung Neoplasms Microenvironment Databases Factual Somatic cell Mutant Adenocarcinoma of Lung medicine.disease_cause Diseases of the respiratory system Immune system Tumor Microenvironment Medicine Humans RNA-Seq TP53 Receptor Gene TP53 Gene Mutation Aged Genetics Mutation Genome RC705-779 business.industry Gene Expression Profiling Research Middle Aged Immune Checkpoint Proteins Gene Expression Regulation Neoplastic Female Tumor Suppressor Protein p53 business Carcinogenesis |
| Zdroj: | BMC Pulmonary Medicine, Vol 21, Iss 1, Pp 1-13 (2021) BMC Pulmonary Medicine |
| ISSN: | 1471-2466 |
| Popis: | Background Differences in genetics and microenvironment of LUAD patients with or without TP53 mutation were analyzed to illustrate the role of TP53 mutation within the carcinogenesis of LUAD, which will provide new concepts for the treatment of LUAD. Methods In this study, we used genetics and clinical info from the TCGA database, including somatic mutations data, RNA-seq, miRNA-seq, and clinical data. More than one bioinformatics tools were used to analyze the unique genomic pattern of TP53-related LUAD. Results According to TP53 gene mutation status, we divided the LUAD patients into two groups, including 265 in the mutant group (MU) and 295 in the wild-type group (WT). 787 significant somatic mutations were detected between the groups, including mutations in titin (TTN), type 2 ryanodine receptor (RYR2) and CUB and Sushi multiple domains 3(CSMD3), which were up-regulated in the MU. However, no significant survival difference was observed. At the RNA level, we obtained 923 significantly differentially expressed genes; in the MU, α-defensin 5(DEFA5), pregnancy-specific glycoprotein 5(PSG5) and neuropeptide Y(NPY) were the most up-regulated genes, glucose-6-phosphatase (G6PC), alpha-fetoprotein (AFP) and carry gametocidal (GC) were the most down-regulated genes. GSVA analysis revealed 30 significant pathways. Compared with the WT, the expression of 12 pathways in the mutant group was up-regulated, most of which pointed to cell division. There were significant differences in tumor immune infiltrating cells, such as Macrophages M1, T cells CD4 memory activated, Mast cells resting, and Dendritic cells resting. In terms of immune genes, a total of 35 immune-related genes were screened, of which VGF (VGF nerve growth factor inducible) and PGC (peroxisome proliferator-activated receptor gamma coactivator) were the most significant up-regulated and down-regulated genes, respectively. Research on the expression pattern of immunomodulators found that 9 immune checkpoint molecules and 6 immune costimulatory molecules were considerably wholly different between the two groups. Conclusions Taking the mutant group as a reference, LUAD patients in the mutant group had significant differences in somatic mutations, mRNA-seq, miRNA-seq, immune infiltration, and immunomodulators, indicating that TP53 mutation plays a crucial role in the occurrence and development of LUAD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink