Comparison of tumor related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma

Abstract

BackgroundThis study compared tumor‐related signaling pathways with known compounds to determine potential agents for lung adenocarcinoma (LUAD) treatment.MethodsKyoto Encyclopedia of Genes and Genomes signaling pathway analyses were performed based on LUAD differentially expressed genes from The Cancer Genome Atlas (TCGA) project and genotype‐tissue expression controls. These results were compared to various known compounds using the Connectivity Mapping dataset. The clinical significance of the hub genes identified by overlapping pathway enrichment analysis was further investigated using data mining from multiple sources. A drug‐pathway network for LUAD was constructed, and molecular docking was carried out.ResultsAfter the integration of 57 LUAD‐related pathways and 35 pathways affected by small molecules, five overlapping pathways were revealed. Among these five pathways, the p53 signaling pathway was the most significant, with CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1 being identified as hub genes. The p53 signaling pathway is implicated as a risk factor for LUAD tumorigenesis and survival. A total of 88 molecules significantly inhibiting the five LUAD‐related oncogenic pathways were involved in the LUAD drug‐pathway network. Daunorubicin, mycophenolic acid, and pyrvinium could potentially target the hub gene CHEK1 directly.ConclusionOur study highlights the critical pathways that should be targeted in the search for potential LUAD treatments, most importantly, the p53 signaling pathway. Some compounds, such as ciclopirox and AG‐028671, may have potential roles for LUAD treatment but require further experimental verification.

Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers

“…It is known that apoptosis is highly regulated and plays an important role in immune response and tumorigenesis ( 70 , 71 ). The p53 signaling pathway is recognized as a potential risk factor in lung adenocarcinoma tumorigenesis and survival ( 72 ). The observed up-regulation in the p53 signaling pathways suggests potential pathogenic functions of these salivary microbiota.…”

High DSCC1 Level Predicts Poor Prognosis of Lung Adenocarcinoma

“…In one study, up-regulation of central genes (CCNB1, CCNB2, CDK1, CDKN2A, and CHEK1) in the p53 signaling pathway confirmed the p53 signaling pathway as a risk factor for tumorigenesis and survival in LUAD. 36 In addition, the abnormality of the cell cycle pathway accelerates the occurrence of LUAD. Some scholars have found that the p53 gene has an important regulatory role in the cell cycle, apoptosis, and genomic stability.…”

Connectivity Mapping: Methods and Applications

“…Following the path set by the CMap 1.0 framework, many drug repositioning studies utilized the resource in a similar way. CMap 1.0 was directly used to reposition drugs for obesity (10), ovarian cancer (11), breast cancer (12), influenza (13), cigarette smoke-induced inflammation (14), gastric cancer (15), inflammatory bowel disease (16), osteogenic differentiation (17), lung adenocarcinoma (18,19), skeletal muscle atrophy (20), and renal cell carcinoma (21); to find compounds with estrogenic activity (22); to induce bone anabolism (17,23); to target cancer stemness (24); and to find radiosensitizing agents for treating lung cancer (25). In most of these studies, the identified drugs and small molecules were experimentally validated in vitro, and in some cases in animal models.…”