Genome-wide haplotype association study identifies risk genes for non-small cell lung cancer

Teng, Yanbo; Ding, Yanjun; Zhang, Mingming; Chen, Xinren; Wang, Xizi; Yu, Hang; Liu, Chonghui; Lv, Hongchao; Zhang, Ruijie

doi:10.1016/j.jtbi.2018.08.007

Cited by 11 publications

(4 citation statements)

References 37 publications

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“…In addition, ESR1 encodes an estrogen receptor involved in hormone binding, DNA binding, and transcription activation and participates in breast cancer, endometrial cancer, osteoporosis, and other pathological processes. ESR1 mRNA overexpression is associated with the prognosis of NSCLC ( Teng et al, 2018 ). The existence of a ligand-independent ESR signaling pathway has been demonstrated, wherein ESR and its functional pathways are subject to multiple regulations such as those of the growth and differentiation of target cells, either through their own phosphorylation or through binding or interaction with different growth factors, co-regulators, oncogenes, or oncogenic proteins ( Zhang et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

et al. 2021

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Background: In recent years, the incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. Shan Ci Gu is commonly used as an anticancer drug in traditional Chinese medicine; however, its specific mechanism against NSCLC has not yet been elucidated. Here, the mechanism was clarified through network pharmacology and molecular docking.Methods: The Traditional Chinese Medicine Systems Pharmacology database was searched for the active ingredients of Shan Ci Gu, and the relevant targets in the Swiss Target Prediction database were obtained according to the structure of the active ingredients. GeneCards were searched for NSCLC-related disease targets. We obtained the cross-target using VENNY to obtain the core targets. The core targets were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins database, and Cytoscape software was used to operate a mesh chart. R software was used to analyze the Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The core targets and active compounds were molecularly docked through Auto-Dock Vina software to predict the detailed molecular mechanism of Shan Ci Gu for NSCLC treatment. We did a simple survival analysis with hub gene to assess the prognosis of NSCLC patients.Results: Three compounds were screened to obtain 143 target genes and 1,226 targets related to NSCLC, of which 56 genes were related to NSCLC treatment. Shan Ci Gu treatment for NSCLC involved many BPs and acted on main targets including epidermal growth factor receptor (EGFR), ESR1, and SRC through signaling pathways including the endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways. Shan Ci Gu might be beneficial for treating NSCLC by inhibiting cell proliferation and migration. Molecular docking revealed that the active compounds β-sitosterol, stigmasterol, and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol had good affinity with the core target genes (EGFR, SRC, and ESR1). Core targets included EGFR, SRC, ESR1, ERBB2, MTOR, MCL1, matrix metalloproteinase 2 (MMP2), MMP9, KDR, and JAK2. Key KEGG pathways included endocrine resistance, EGFR tyrosine kinase inhibitor resistance, ErbB signaling, PI3K-Akt signaling, and Rap1 signaling pathways. These core targets and pathways have an inhibitory effect on the proliferation of NSCLC cells.Conclusion: Shan Ci Gu can treat NSCLC through a multi-target, multi-pathway molecular mechanism and effectively improve NSCLC prognosis. This study could serve as a reference for further mechanistic research on wider application of Shan Ci Gu for NSCLC treatment.

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Section: Discussionmentioning

confidence: 99%

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

et al. 2021

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“…The results also indicated that a comparative evaluation of methylation ratios before and after surgery might be a powerful tool for predicting the prognosis of lung cancer patients [ 57 ]. Simultaneously, it was suggested that ESR1 mRNA overexpression is innately associated with NSCLC prognosis [ 58 ]. Therefore, ESR1 could also become an important key target for treating NSCLC, which is consistent with the results of Wang et al [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Utilizing Bioinformatics Technology to Explore the Potential Mechanism of Danggui Buxue Decoction against NSCLC

Sohail

et al. 2022

Disease Markers

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While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients ( p < 0.05 ). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.

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“…Several applications have been developed to allow genes to be linked with complex diseases [26][27][28][29][30][31] . One of them is Génie, which has been previously used in the determination of risk genes for non-small cell lung cancer 32 . Using this tool, we obtained a set close to 1,000 genes coding for proteins related to OLP, among which chemokine and cytokine-mediated inflammation stand out.…”

Section: Discussionmentioning

confidence: 99%

Oral lichen planus interactome reveals CXCR4 and CXCL12 as candidate therapeutic targets

Rivera

Crisóstomo

Peña

et al. 2020

Sci Rep

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Today, we face difficulty in generating new hypotheses and understanding oral lichen planus due to the large amount of biomedical information available. In this research, we have used an integrated bioinformatics approach assimilating information from data mining, gene ontologies, protein-protein interaction and network analysis to predict candidate genes related to oral lichen planus. A detailed pathway analysis led us to propose two promising therapeutic targets: the stromal cell derived factor 1 (CXCL12) and the C-X-C type 4 chemokine receptor (CXCR4). We further validated our predictions and found that CXCR4 was upregulated in all oral lichen planus tissue samples. Our bioinformatics data cumulatively support the pathological role of chemokines and chemokine receptors in oral lichen planus. From a clinical perspective, we suggest a drug (plerixafor) and two therapeutic targets for future research. Oral lichen planus (OLP) is a chronic immunologically mediated disease 1. Histopathological features of OLP include hyperkeratosis, acanthosis, degeneration by liquefaction of the basal keratinocyte layer, and prominent lymphocyte infiltration at the connective tissue-epithelium interface 2. OLP is not a homogeneous clinical entity, but a complex disease. A recent review proposes a new classification of this disease, taking into consideration a set of lesions with similar characteristics, including oral lichenoid contact lesions, oral lichenoid drug reactions, and lichen planus pemphigoides, among others 3 .The clinical findings vary from white reticular plaques to erythema, erosions, ulceration, and hyperkeratotic plaques in the oral mucosa 4. Although reticular lesions are often asymptomatic, burning or pain often accompanies erosive/ulcerative manifestations of OLP. The severity of pain may vary from mild to severe and may even interfere with patients' speech, feeding, and swallowing 4. According to the WHO, this disease has a potential for cancerization 5. This potential is presented in about 1% of patients 6. Despite the efforts in biomedical research, the etiology of OLP is unknown, and its molecular basis is still unclear. This may explain why the treatment is palliative. For these reasons, exploration of the mechanisms that govern the disease's pathophysiological process is needed. A disease is rarely the result of an abnormality in a single gene, but it reflects disturbances in the complex intracellular and intercellular network that links tissue and organ systems 7. Today, we face difficulty in generating new hypotheses and understanding OLP due to the large amount of biomedical information available. Encapsulating that information in an understandable way is one of the current challenges of network-based approaches to the study of human diseases 8. The heterogeneity of pathologies, the difficulty of finding a gene or protein in a certain localization, and the cost involved in experimental studies have led to the development of several in silico approaches for the identification of genes and proteins assoc...

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Genome-wide haplotype association study identifies risk genes for non-small cell lung cancer

Cited by 11 publications

References 37 publications

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

Utilizing Bioinformatics Technology to Explore the Potential Mechanism of Danggui Buxue Decoction against NSCLC

Oral lichen planus interactome reveals CXCR4 and CXCL12 as candidate therapeutic targets

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