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pmid:36111050

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling-a bioinformatic analysis.

Shuying Wang · Xiaoxing Liang · Ruomi Guo · Jiao Gong · Xiaolong Zhong · Yulin Liu · Deqing Wang · Yanmei Hao · Bo Hu

Annals of translational medicine · 2022 doi:10.21037/atm-22-3340

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling-a bioinformatic analysis.
doi
10.21037/atm-22-3340
pmid
36111050
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[0]
Shuying Wang
[1]
Xiaoxing Liang
[2]
Ruomi Guo
[3]
Jiao Gong
[4]
Xiaolong Zhong
[5]
Yulin Liu
[6]
Deqing Wang
[7]
Yanmei Hao
[8]
Bo Hu
journal
Annals of translational medicine
year
2022
abstract
Background: Molecular typing based on deoxyribonucleic acid (DNA) methylation and gene expression can extend understandings of the molecular mechanisms involved in lung adenocarcinoma (LUAD) and enhance current diagnostic, treatment, and prognosis prediction approaches. Methods: Gene expression and DNA methylation data sets of LUAD were obtained from The Cancer Genome Atlas (TCGA), and the differential gene and methylation expression levels were analyzed. Results: We successfully divided the LUAD samples into 2 clinically relevant subtypes with significantly different survival times and tumor stages according to the transcriptome and methylation data. We found significant differences in the survival status, age, gender, tumor stage, node stage, and clinical stage between the 2 subtypes. The hub genes identified in the subnetworks, including NCAPG, CCNB1, DLGAP5, HLA-DQA1, HLA-DPA1, HLA-DPB1, SFTP, SCGBA1A, and SFTPD, were correlated with the cell cycle and immune system. The Gene Ontology annotation of the hub genes showed that the biological processes included organelle fission mitotic nuclear division, and sister chromatid segregation. The cellular components included chromosomal region, spindle, and kinetochore. The molecular functions included tubulin-binding, microtubule-binding, and DNA replication origin binding. The Kyoto Encyclopedia of Genes and Genomes signaling pathways related to the hub genes mainly included the cell cycle, human T-cell leukemia virus (type 1) infection, inflammatory bowel disease, and the intestinal immune network for immunoglobulin A production. The clinical stage difference was also confirmed in the validation group using the GSE32863 data set. Conclusions: Our findings extend understandings of the pathogenesis of LUAD and can be used to improve current diagnosis, treatment, and prognosis prediction strategies.
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The LUAD samples were also classified into different subtypes using the non-negative matrix factorization (NMF) method using the R package CancerSubtypes.
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We found significant differences in the survival status, age, gender, tumor stage, node stage, and clinical stage between the 2 subtypes. The hub genes identified in the subnetworks, including NCAPG, CCNB1, DLGAP5, HLA-DQA1, HLA-DPA1, HLA-DPB1, SFTP, SCGBA1A, and SFTPD, were correlated with the cell cycle and immune system. The Gene Ontology annotation of the hub genes showed that the biological processes included organelle fission mitotic nuclear division, and sister chromatid segregation. The cellular components included chromosomal region, spindle, and kinetochore. The molecular functions included tubulin-binding, microtubule-binding, and DNA replication origin binding. The Kyoto Encyclopedia of Genes and Genomes signaling pathways related to the hub genes mainly included the cell cycle, human T-cell leukemia virus (type 1) infection, inflammatory bowel disease, and the intestinal immune network for immunoglobulin A production. 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