scholarly journals Expression and Regulatory Network Analysis of MiR-139-3p, a New Potential Serum Biomarker for Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis

2020 ◽  
Vol 19 ◽  
pp. 153303382092096
Author(s):  
Yonghong Wang ◽  
Qimei Fang ◽  
Liru Tian ◽  
Zhongzhen Yuan ◽  
Lizhen Tian ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Esophageal Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Cancer Genome Atlas

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.

scholarly journals Diagnosis value of aberrantly expressed microRNA profiles in lung squamous cell carcinoma: a study based on the Cancer Genome Atlas

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e4101 ◽  
Author(s):  
Sheng Yang ◽  
Jing Sui ◽  
Geyu Liang
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Lung Squamous Cell Carcinoma ◽  
Clinical Information ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Background Lung cancer is considered as one of the most frequent and deadly cancers with high mortality all around the world. It is critical to find new biomarkers for early diagnosis of lung cancer, especially lung squamous cell carcinoma (LUSC). The Cancer Genome Atlas (TCGA) is a database which provides both cancer and clinical information. This study is a comprehensive analysis of a novel diagnostic biomarker for LUSC, based on TCGA. Methods and Results The present study investigated LUSC-specific key microRNAs (miRNAs) from large-scale samples in TCGA. According to exclusion criteria and inclusion criteria, the expression profiles of miRNAs with related clinical information of 332 LUSC patients were obtained. Most aberrantly expressed miRNAs were identified between tumor and normal samples. Forty-two LUSC-specific intersection miRNAs (fold change >2, p < 0.05) were obtained by an integrative computational method, among them six miRNAs were found to be aberrantly expressed concerning characteristics of patients (gender, lymphatic metastasis, patient outcome assessment) through Student t-test. Five miRNAs correlated with overall survival (log-rank p < 0.05) were obtained through the univariate Cox proportional hazards regression model and Mantel–Haenszel test. Then, five miRNAs were randomly selected to validate the expression in 47 LUSC patient tissues using quantitative real-time polymerase chain reaction. The results showed that the test findings were consistent with the TCGA findings. Also, the diagnostic value of the specific key miRNAs was determined by areas under receiver operating characteristic curves. Finally, 577 interaction mRNAs as the targets of 42 LUSC-specific intersection miRNAs were selected for further bioinformatics analysis. Conclusion This study indicates that this novel microRNA expression signature may be a useful biomarker of the diagnosis for LUSC patients, based on bioinformatics analysis.

scholarly journals Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhimin Shen ◽  
Mingduan Chen ◽  
Fei Luo ◽  
Hui Xu ◽  
Peipei Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Differential Expression Analysis ◽  
Biological Significance ◽  
The Cancer Genome Atlas ◽  
Paclitaxel Resistance ◽  
Bioinformatics Analyses ◽  
Key Genes

Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.

Analysis of Key Pathways, Genes and Immune Cell Infiltration in Metastatic Esophageal Squamous Cell Carcinoma Based on Bioinformatics

2021 ◽  
Author(s):  
Zhangjiao Wang ◽  
Yong Shen ◽  
Qingxia Xu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Markers ◽  
Squamous Cell ◽  
Protein Interaction ◽  
Signal Pathway ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Geo Database

Abstract Objective: To seek potential metastatic tumor markers in esophageal squamous cell carcinoma (ESCC) by bioinformatics. Methods: Four datasets (GSE70409, GSE26886, GSE161533, GSE17351) were downloaded from GEO database, and the differential expression of mRNA was screened by Limma software package. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation; Protein–protein interaction network of these DEGs was constructed based on STRING database; then, the hub gene were identified by six algorithms of Cytoscape software. Using GEPIA2 database and OncoLnc database to analyze the survival of hub genes. Immune infiltration was analyzed by TIMER2 database and CIBERSORT deconvolution method. Results: A total of 244 differentially expressed genes(DEGs)were screened from 4 data sets of GEO database, including 164 up-regulated genes and 80 down-regulated genes, which were mainly enriched at extracellular region and extracellular space, and involved in biological processes such as cell adhesion and proteolysis related to tumor invasion and metastasis. KEGG results showed that DEGs were mainly enriched in PI3K-Akt signal pathway and extracellular matrix (ECM) receptor interaction signal pathway. Through the protein interaction analysis of DEGs, we found that three hub genes (CXCL8, MMP9 and MMP13) were highly expressed in ESCC. However, the GEPIA2 database shows that only CXCL8 is associated with the overall survival of ESCC patients. The results of immune infiltration showed that macrophages and resting dendritic cells increased significantly, while mast cells and monocytes decreased significantly. Conclusion: Three hub genes and immune infiltrating cells may play an important role in ESCC, and are expected to become potential tumor markers of ESCC and be used in the diagnosis and treatment of ESCC.

Genomic Landscape of Squamous Cell Carcinoma of the Lung

2013 ◽  
pp. 348-353
Author(s):  
Daniel Morgensztern ◽  
Siddhartha Devarakonda ◽  
Ramaswamy Govindan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Targets ◽  
The Cancer Genome Atlas ◽  
Molecular Alterations ◽  
The Past ◽  
Genomic Landscape ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Outcomes with standard therapy for patients with advanced squamous cell carcinoma (SQCC) of the lung have not improved significantly over the past decade using a predominantly empiric approach. Recent advances in pulmonary adenocarcinomas (ACs) have allowed the subdivision according to molecular subsets and the identification of specific molecular alterations that predict significant benefit from specific targeted therapies. Genomic alterations reported by The Cancer Genome Atlas (TCGA) Project identified a number of molecular targets that need to be studied systematically to improve the overall survival of patients with SQCC of the lung.

scholarly journals Auraptene Attenuates Malignant Properties of Esophageal Stem-Like Cancer Cells

2016 ◽  
Vol 16 (4) ◽  
pp. 519-527 ◽  
Author(s):  
Saffiyeh Saboor-Maleki ◽  
Fatemeh B. Rassouli ◽  
Maryam M. Matin ◽  
Mehrdad Iranshahi
Keyword(s):  
Polymerase Chain Reaction ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Esophageal Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Real Time ◽  
Squamous Cell ◽  
Chain Reaction ◽  
Polymerase Chain

The high incidence of esophageal squamous cell carcinoma has been reported in selected ethnic populations including North of Iran. Low survival rate of esophageal carcinoma is partially due to the presence of stem-like cancer cells with chemotherapy resistance. In the current study, we aimed to determine the effects of auraptene, an interesting dietary coumarin with various biological activities, on malignant properties of stem-like esophageal squamous cell carcinoma, in terms of sensitivity to anticancer drugs and expression of specific markers. To do so, the half maximal inhibitory concentration values of auraptene, cisplatin, paclitaxel, and 5-fluorouracil were determined on esophageal carcinoma cells (KYSE30 cell line). After administrating combinatorial treatments, including nontoxic concentrations of auraptene + cisplatin, paclitaxel, or 5-fluorouracil, sensitivity of cells to chemical drugs and also induced apoptosis were assessed. In addition, quantitative real-time polymerase chain reaction was used to study changes in the expression of tumor suppressor proteins 53 and 21 ( P53 and P21), cluster of differentiation 44 ( CD44), and B cell-specific Moloney murine leukemia virus integration site 1 ( BMI-1) upon treatments. Results of thiazolyl blue assay revealed that auraptene significantly ( P < .05) increased toxicity of cisplatin, paclitaxel, and 5-fluorouracil in KYSE30 cells, specifically 72 hours after treatment. Conducting an apoptosis assay using flow cytometry also confirmed the synergic effects of auraptene. Results of quantitative real-time polymerase chain reaction revealed significant ( P < .05) upregulation of P53 and P21 upon combinatorial treatments and also downregulation of CD44 and BMI-1 after auraptene administration. Current study provided evidence, for the first time, that auraptene attenuates the properties of esophageal stem-like cancer cells through enhancing sensitivity to chemical agents and reducing the expression of CD44 and BMI-1 markers.

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