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.

Background: Previous studies have shown that human crystallin alpha B (CRYAB) is highly expressed in human cancers and associated with poor survival in cancer patients. Here we investigated whether SLC39A11 and CRYAB genes were related to the proliferation and development of lung adenocarcinoma (LUAD) to explore their potential as therapeutic targets and prognostic markers for LUAD. Methods: CRYAB and SLC39A11 genes were identified from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The human lung cancer cell lines A549 and H1975 were cultured, transfected, and subjected to RNA extraction. After genomic DNA removal, the RNA was reversetranscribed. Differences between 2 groups were compared using t-test.Results: Knockdown of SLC39A11 inhibited the proliferation of LUAD cells in A549 and H1975.Knockdown of CRYAB promoted the increase of LUAD cell clones, while knockdown of SLC39A11 suppressed LUAD cell clones. In both A549 and H1975 cell lines, knockout of CRYAB inhibited the apoptosis of LUAD cells, whereas knockout of SLC39A11 promoted the apoptosis of LUAD cells. In the H1975 cell line, knockout of CRYAB also lowered the proportion of cells in interphase and increased the proportion of mitotic cells, while knockout of SLC39A11 also slowed down the division cycle of tumor cells.Knockdown of CRYAB promoted the migration of LUAD cells in both the A549 cell line and H1975 cell line. In the H1975 cell line, knockout of SLC39A11 also reduced the invasive ability of LUAD cells.Conclusions: CRYAB and SLC39A11 could be used as prognostic indicators and therapeutic targets for LUAD.