Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Copy number variation of some gene loci in lung tumor cells extracted by laser capture microdissection and in cell-free DNA in the plasma of patients with lung cancer was analyzed for identification of potential molecular markers. Tissue specimens fixed in formalin and embedded in paraffin blocks (FFPE-blocks) from 90 patients and extracellular DNA from plasma samples of 70 patients and 30 donors were used. Copy number variation was assayed for 30 genes (BAX, BCL2, C-FLAR, P53, MDM2, CASP9, CASP3, CASP8, SOX2, OCT4, PIK3, MKI67, HV2, HIF1A1, XRCC1, MMP1, TERT, CTNNB1, KRAS, EGFR, GRB2, SOS1, MAPK1, STAT1, BRAF, FTO, and mir3678) and reference loci (ACTB, B2M, and GAPDH) by the real-time quantitative PCR. Changed copy numbers were detected for genes responsible for apoptosis regulation (BAX, P53, and CASP3), proliferation (SOX2), DNA reparation (XRCC1), oxidative phosphorylation (HV2), EGFR signaling pathway (GRB2, SOS1, MAPK1, STAT1, and BRAF), and for mir3678 gene in lung tumor cells and extracellular DNA.
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PMID:Copy Number Variation in Tumor Cells and Extracellular DNA in Patients with Lung Adenocarcinoma. 3165 98

Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated remarkable treatment efficacy in advanced non-small cell lung cancer (NSCLC). However, low expression of programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) wild-type NSCLCs are refractory, and only few therapeutic options exist. Currently, combination therapy with ICIs is frequently used in order to enhance the treatment response rates. Yet, this regimen is still associated with poor treatment outcome. Therefore, identification of potential therapeutic targets for this subgroup of NSCLC is strongly desired. Here, we report the distinct methylation signatures of this special subgroup. Moreover, several druggable targets and relevant drugs for targeted therapy were incidentally identified. We found hypermethylated differentially methylated regions (DMRs) in three regions (TSS200, TSS1500, and gene body) are significantly higher than hypomethylated ones. Downregulated methylated genes were found to be involved in negative regulation of immune response and T cell-mediated immunity. Moreover, expression of four methylated genes (PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), BAIAP2L2 (BAR/IMD Domain Containing Adaptor Protein 2 Like 2), NPR3 (Natriuretic Peptide Receptor 3), SNX10 (Sorting Nexin 10)) can influence patients' prognosis. Subsequently, based on DrugBank data, NetworkAnalyst 3.0 was used for protein-drug interaction analysis of up-regulated differentially methylated genes. Protein products of nine genes were identified as potential druggable targets, of which the tumorigenic potential of XDH (Xanthine Dehydrogenase), ATIC (5-Aminoimidazole-4-Carboxamide Ribonucleotide Formyltransferase/IMP Cyclohydrolase), CA9 (Carbonic Anhydrase 9), SLC7A11 (Solute Carrier Family 7 Member 11), and GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) have been demonstrated in previous studies. Next, molecular docking and molecular dynamics simulation were performed to verify the structural basis of the therapeutic targets. It is noteworthy that the identified pemetrexed targeting ATIC has been recently approved for first-line use in combination with anti-PD1 inhibitors against lung cancer, irrespective of PD-L1 expression. In future work, a pivotal clinical study will be initiated to further validate our findings.
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PMID:Combined Methylome and Transcriptome Analyses Reveals Potential Therapeutic Targets for EGFR Wild Type Lung Cancers with Low PD-L1 Expression. 3289 91

Lung cancer is one of the leading triggers for cancer death worldwide. In this study, the relationship of the aberrantly methylated and differentially expressed genes in lung adenocarcinoma (LUAD) with cancer prognosis was investigated, and 5 feature genes were identified eventually. Specifically, we firstly downloaded the LUAD-related mRNA expression profile (including 57 normal tissue samples and 464 LUAD tissue samples) and Methy450 expression data (including 32 normal tissue samples and 373 LUAD tissue samples) from the TCGA database. The package "limma" was used to screen differentially expressed genes and aberrantly methylated genes, which were intersected for identifying the hypermethylated downregulated genes (DGs Hyper) and the hypomethylated upregulated genes (UGs Hypo). GO annotation and KEGG pathway enrichment analysis were further performed, and it was found that these DGs Hyper and UGs Hypo were predominantly activated in the biological processes and signaling pathways such as the regulation of vasculature development, DNA-binding transcription activator activity, and Ras signaling pathway, indicating that these genes play a vital role in the initiation and progression of LUAD. Additionally, univariate and multivariate Cox regression analyses were conducted to find the genes significantly associated with LUAD prognosis. Five genes including SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 were identified, with the former three highly expressed and the latter two poorly expressed in LUAD, indicating poor prognosis of LUAD patients as judged by survival analysis.
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PMID:Aberrant Methylation and Differential Expression of SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 Are Associated with the Prognosis of Lung Adenocarcinoma. 3302 90


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