The Pharmacogenomics “Side-effect” of TP53/EGFR in Non-small Cell Lung Cancer Accompanied with Atorvastatin Therapy: A Functional Network Analysis

2020 ◽  
Vol 19 (17) ◽  
pp. 2060-2071
Author(s):  
Lei Zhang ◽  
Yifang Huang ◽  
Xuedong Gan ◽  
Siying He ◽  
Xiaohuan Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kegg Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Atorvastatin Therapy ◽  
Drugbank Database

Background: Atorvastatin belongs to the group of statins and is the leading drug for hypercholesterolemia treatment. Although, its anticancer effects are highly appreciated, its properties are still unclear. The aim of this study was to explore the underlying anticancer mechanisms induced by atorvastatin and enlarge the potential target in non-small cell lung cancer. Methods: arget genes of atorvastatin were collected by the DrugBank database. Prediction of interaction between primary targets and secondary targets was performed, and protein-protein interaction network was constructed though the STRING. Then, KEGG pathway enrichment analysis was performed with WebGestalt and ClueGO, including the pathways in non-small cell lung cancer. Furthermore, a genomic alteration analysis of the selected seed genes of atorvastatin benefit and non-small cell lung cancer pathway was conducted by cBioPortal. Finally, a survival analysis with the selected seed genes in lung cancer (lung adenocarcinoma, lung squamous cell carcinoma) was conducted using Kaplan-Meier (KM) plotter. Results: To identify seed genes, 65 potential candidate genes were screened as targets for atorvastatin using STRING with DrugBank database, while the KEGG pathway was enriched to get the overlap match of pathways in non-small cell lung cancer. Then 4 seed genes, Epidermal Growth Factor Receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), AKT serine/threonine kinase 1 (AKT1) and tumor protein p53 (TP53), were selected and their genomic alternation were evaluated by cBioPortal. Survival analysis found that TP53 and EGFR showed a significant correlation (log rank P = 3e-07 and 0.023) with lung adenocarcinoma and lung squamous cell carcinoma, according to the KM analysis. Conclusion: Gene-phenotype connectivity for atorvastatin in non-small cell lung cancer was identified using functional/activity network analysis method, and our findings demonstrated that TP53 and EGFR could be the potential targets in cancer patients with atorvastatin therapy.

scholarly journals Identification of a Ferroptosis-related lncRNA Signature for Prognosis Prediction in Lung Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Jiahao Cai ◽  
Jie Gu ◽  
Di Ge ◽  
Fengkai Xu
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
Small Cell Lung

Abstract BACKGROUNDThe incidence of lung cancer ranks first among malignant tumors all over the world. Based on the histological features, lung cancer could be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), of which non-small cell lung cancer accounts for about 80%. NSCLC mainly includes lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and large cell lung cancer (LLC). Most of the patients were diagnosed at a late stage, which means the 5-year overall survival rate for patients was shallow. According to the situation, new biomarkers are needed to recognize patients at high risk, which would help give them appropriate treatment to improve their outcomes.Ferroptosis, an important iron-dependent cell death driven by oxidative phospholipid damage and characterized by lipid peroxidation, was recently found to play a novel role in several cancers. Existing research have identified many genes related to ferroptosis in tumor tissues. However, research on ferroptosis-genes-related long non-coding RNA (lncRNA) in lung cancer is still insufficient. METHODSWe acquired the statistics from the public database TCGA Lung Squamous Cell Carcinoma (LUSC). Then a multi-lncRNA signature was constructed to recognize patients at high risk based on differentially expressed ferroptosis-genes-related lncRNAs in lung squamous cell carcinoma. RESULTSWe finally identified eight differently expressed ferroptosis-genes-related lncRNAs are predictive of outcomes in LUSC patients. Kaplan-Meier analyses revealed that the high-risk-related lncRNAs signature has strong predictive power for poor LUSC prognosis (AUC=0.686). Our risk-predictive model was superordinate to the traditional predictive method based on clinicopathological characteristics (Stage, AUC=0.563). Gene set enrichment analysis (GSEA) revealed signaling pathways that ferroptosis-genes-related lncRNAs may participate in. Further study of immune function-related gene sets showed that parainflammation, APC co-stimulation, inflammation-promoting, T cell co-stimulation, Type I and type II INF response were significantly associated with risk-related lncRNAs signature. Immune checkpoint-related genes such as PDCD-1, CD70, CD28, and CD27, etc., also expressed differently between the two risk groups.CONCLUSIONThe specific differentially expressed ferroptosis-related lncRNAs have a strong predictive effect on the prognosis in patients with lung squamous cell carcinoma.

A re-evaluation of squamous cell carcinoma antigen (SCC) as a serum marker for non-small cell lung cancer

2007 ◽  
Vol 25 (2) ◽  
pp. 187-189 ◽  
Author(s):  
Katsunori Kagohashi ◽  
Hiroaki Satoh ◽  
Hiroichi Ishikawa ◽  
Morio Ohtsuka ◽  
Kiyohisa Sekizawa
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Serum Marker ◽  
Small Cell ◽  
Squamous Cell Carcinoma Antigen ◽  
Small Cell Lung

scholarly journals Epidemiologic trends in lung cancer over two decades in Northern Greece: an analysis of bronchoscopic data

2016 ◽  
Vol 71 (4) ◽  
Author(s):  
T. Kontakiotis ◽  
N. Manolakoglou ◽  
F. Zoglopitis ◽  
D. Iakovidis ◽  
L. Sacas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Northern Greece ◽  
Female Ratio

Background and Aim. The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. Methods. From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. Results. Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8±9.4 vs. 62.1±8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p<0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p<0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p<0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. Conclusion. The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.

scholarly journals Co-expression Network and Prognosis Analyses of Pyroptosis-related Genes in Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Zixiao Liu ◽  
Xudong Liu ◽  
Yu Zhang ◽  
Yongjie Zhou ◽  
Shuaibin Lian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hydrophobic Interactions ◽  
Tumor Staging ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
Differentially Expressed ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Lung cancer is very difficult to diagnose in the its early stages because of its initial asymptomatic characteristics. In recent years, pyrolysis has been shown identified as a novel type of programmed cell death with inflammation mediated by the gasdermin family. In this study, 33 differentially-expressed pyroptosis-related genes were commonly identified in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. Tumor-related gasdermin family genes that were significantly differentially expressed in non-small cell lung cancer (NSCLC) tissues were identified by our co-expression network analysis. Among them, the mRNA level of GSDMB gene had significant impacts on tumor staging and survival rates of NSCLC patients. Therefore, this gene is a potential new therapeutic target for the treatment of NSCLC. In addition, the high expression levels of GSDMC/D were significantly correlated with the low overall survival (OS), progression-free survival (FP) and post-progression survival (PPS) of NSCLC patients. Therefore, this gene is a potential oncogene for NSCLC. Furthermore, four small molecules (erastin, cefotiam, metanephrine, and vorinostat) that could most significantly reverse the NSCLC gene expression were identified. They interacted with GSDMB proteins mainly through H-bonds and hydrophobic interactions. This study provides new therapeutic targets and prognostic makers for NSCLC patients.

scholarly journals Mutation profile of non-small cell lung cancer revealed by next generation sequencing

2020 ◽  
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Yu-Chia Chen ◽  
Ting-Yuan Liu ◽  
Ya-Ting Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Whole Exome

Abstract Background: Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method: We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients. Results: Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.Conclusions: We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.

Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases

2016 ◽  
Vol 23 (1) ◽  
pp. 151-156 ◽  
Author(s):  
Judit Moldvay ◽  
Katalin Fábián ◽  
Márta Jäckel ◽  
Zsuzsanna Németh ◽  
Krisztina Bogos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Prognostic Factor ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung
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