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

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.

Prognostic factors and genetic markers in thymic epithelial tumors: A narrative review

“…Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription 52,53 . Consequently, DNA methylation has a role in carcinogenesis.…”

“…When located in a gene promoter, DNA methylation typically acts to repress gene transcription. 52 , 53 Consequently, DNA methylation has a role in carcinogenesis. Bi et al investigated the DNA methylation status of A and B thymomas.…”

Thymic epithelial tumours: histopathological classification and differential diagnosis

“…For instance, Tang et al . showed that two metabolism‐related genes (MRGs), ASNS and BLVRA were strongly correlated with survival in TET, 164 and Hou et al . revealed that lower expression of HMGB1, a proinflammatory cytokine‐related gene, is seen in thymic carcinomas compared to thymoma, and correlates with a poor prognosis 165 .…”

“…163 Gene expression profiling may also be correlated with prognosis. For instance, Tang et al showed that two metabolismrelated genes (MRGs), ASNS and BLVRA were strongly correlated with survival in TET, 164 and Hou et al revealed that lower expression of HMGB1, a proinflammatory cytokine-related gene, is seen in thymic carcinomas compared to thymoma, and correlates with a poor prognosis. 165 Higher mutation rates have been seen with advanced stage and more advanced pathological types.…”