scholarly journals Gene set enrichment analysis and meta-analysis to identify six key genes regulating and controlling the prognosis of esophageal squamous cell carcinoma

2018 ◽  
Vol 10 (10) ◽  
pp. 5714-5726 ◽  
Author(s):  
Wenwu He ◽  
Linxin Chen ◽  
Kun Yuan ◽  
Qiuxi Zhou ◽  
Lin Peng ◽  
...  
2021 ◽  
Author(s):  
Hung-Sheng Shih ◽  
Li-Yu Hung ◽  
Ming-Yu Hsieh

Abstract Background: A few recent studies have addressed the function of FN1 (Fibronectin 1) in head and neck cancer. The clinical information from 500 HNSCC (Head and neck squamous cell carcinoma) patients with FN1 gene expression data set was published by The Cancer Genome Atlas (TCGA). The correlation between clinicopathologic characteristics and FN1 expression was analyzed by Logistic regression and Wilcoxon signed rank test. Survival function was performed employing Kaplan-Meier estimator, and the relationship between clinicopathological characteristics, prognostic outcome, and FN1 expression were examined by using Cox regression analysis. As Gene set enrichment analysis (GSEA) was performed, we investigated the correlation between FN1 expression and immune cell infiltrates with single-sample gene set enrichment analysis (ssGSEA). Results: Patients with high FN1 expression revealed a significantly decreased overall survival (OS), and disease-specific survival (DSS) than those with low FN1 expression in Kaplan-Meier survival analyses. According to the above results, univariate and multivariate analysis revealed that patients with high FN1 expression had lower OS than those with low FN1 expression.Conclusions: The findings of this research provide insights for FN1 may be potential prognostic biomarkers for diagnosis as well as therapeutic targets in HNSCC patients.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hong Jin ◽  
Hui Miao ◽  
Yuan-Wen Nie ◽  
Yang-Yang Lin

Abstract Background Oral cavity cancer ranks the sixth most common malignancy worldwide, of which oral squamous cell carcinoma is the predominant type. This study aimed to investigate the function and the underlying mechanism of resistin like beta (RETNLB) in oral squamous cell carcinoma. Methods The data of oral squamous cell carcinoma samples from The Cancer Genome Atlas database was used to examine RETNLB expression and assess its correlation with the clinical outcomes. Biological functions of RETNLB on the growth, invasion and migration of cells were determined by cell counting kit 8, clonogenic growth, and Transwell assays. Gene set enrichment analysis was utilized to identify the important gene sets associated with RETNLB expression, which was further confirmed by western blot. Results We found that RETNLB was upregulated in oral squamous cell carcinoma tissues and cells. High expression of RETNLB was closely linked to age and pathological tumor, and significantly related to poor survival of oral squamous cell carcinoma patients. Further functional experiments showed that knockdown of RETNLB significantly reduced the viability, mobility and invasiveness of cells. Moreover, gene set enrichment analysis suggested that Toll-like receptor signaling pathway was significantly correlated with high RETNLB expression. Further western blot analysis verified that silencing RETNLB could notably suppress the protein levels of Toll-like receptor 2, Toll-like receptor 4 and phosphor- extracellular signal-regulated kinase. Conclusions These results suggested that downregulation of RETNLB may restrain the progression of oral squamous cell carcinoma by inactivating TLR/2/4/ERK pathway.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Qinghua Ji ◽  
Yingying Cai ◽  
Sachin Mulmi Shrestha ◽  
Duo Shen ◽  
Wei Zhao ◽  
...  

Immune checkpoint inhibitor (ICI) therapy may benefit patients with advanced esophageal squamous cell carcinoma (ESCC); however, novel biomarkers are needed to help predict the response of patients to treatment. Differentially expressed immune-related genes within The Cancer Genome Atlas ESCC dataset were selected using the weighted gene coexpression network and lasso Cox regression analyses. Based on these data, an immune-related gene prognostic index (IRGPI) was constructed. The molecular characteristics of the different IRGPI subgroups were assessed using mutation information and gene set enrichment analysis. Differences in immune cell infiltration and the response to ICI therapy and other drugs were also analyzed. Additionally, tumor and adjacent control tissues were collected from six patients with ESCC and the expression of these genes was verified using real-time quantitative polymerase chain reaction. IRGPI was designed based on CLDN1, HCAR3, FNBP1L, and BRCA2, the expression of which was confirmed in ESCC samples. The prognosis of patients in the high-IRGPI group was poor, as verified using publicly available expression data. KMT2D mutations were more common in the high-IRGPI group. Enrichment analysis revealed an active immune response, and immune infiltration assessment showed that the high-IRGPI group had an increased infiltration degree of CD8 T cells, which contributed to the improved response to ICI treatment. Collectively, these data demonstrate that IRGPI is a robust biomarker for predicting the prognosis and response to therapy of patients with ESCC.


2020 ◽  
Vol 22 (1) ◽  
pp. 60
Author(s):  
Sichong Han ◽  
Zhe Wang ◽  
Jining Liu ◽  
Qipeng Yuan

Understanding the mechanism by which sulforaphene (SFE) affects esophageal squamous cell carcinoma (ESCC) contributes to the application of this isothiocyanate as a chemotherapeutic agent. Thus, we attempted to investigate SFE regulation of ESCC characteristics more deeply. We performed gene set enrichment analysis (GSEA) on microarray data of SFE-treated ESCC cells and found that differentially expressed genes are enriched in TNFα_Signaling_via_the_NFκB_Pathway. Coupled with the expression profile data from the GSE20347 and GSE75241 datasets, we narrowed the set to 8 genes, 4 of which (C-X-C motif chemokine ligand 10 (CXCL10), TNF alpha induced protein 3 (TNFAIP3), inhibin subunit beta A (INHBA), and plasminogen activator, urokinase (PLAU)) were verified as the targets of SFE. RNA-sequence (RNA-seq) data of 182 ESCC samples from The Cancer Genome Atlas (TCGA) were grouped into two phenotypes for GSEA according to the expression of CXCL10, TNFAIP3, INHBA, and PLAU. The enrichment results proved that they were all involved in the NFκB pathway. ChIP-seq analyses obtained from the Cistrome database indicated that NFκB-p65 is likely to control the transcription of CXCL10, TNFAIP3, INHBA, and PLAU, and considering TNFAIP3 and PLAU are the most significantly differentially expressed genes, we used chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to verify the regulation of p65 on their expression. The results demonstrated that SFE suppresses ESCC progression by down-regulating TNFAIP3 and PLAU expression in a p65-dependent manner.


2013 ◽  
Vol 50 (2) ◽  
pp. 324-332 ◽  
Author(s):  
Yanyan Tang ◽  
Wenwu He ◽  
Yunfei Wei ◽  
Zhanli Qu ◽  
Jinming Zeng ◽  
...  

2021 ◽  
Author(s):  
zhen wang ◽  
han yang ◽  
rusi zhang ◽  
bin luo ◽  
bingchen xu ◽  
...  

Abstract BackgroundEsophageal squamous cell carcinoma (ESCC) is a kind of digestive system malignant tumor with high morbidity and mortality worldwide. With the rise of immunotherapy applied in cancer treatment, immune-related mechanisms in ESCC and other digestive system carcinomas are in urgent need of being detected.MethodsIn our study, single-sample gene set enrichment analysis (ssGSEA) was performed at first to analyze the expression profile downloaded from NCBI Gene Expression Omnibus (GEO) database. Then via a series of bioinformatic analyses, including Mann-Whitney test, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis and differentially expressed genes (DEGs) analysis, we identified targeting immunocyte and related genes. Finally, we validated the results in TIMER database.ResultsOur analyses showed that macrophage infiltrating level is obviously higher in advanced stages in ESCC compared with other types of immunocytes. MEOX2 was detected as a biomarker correlated with macrophage infiltration in ESCC and other types of digestive system carcinomas. And MEOX2 expression was strongly associated with mRNA expression of colony-stimulating factor 1 (CSF-1) and CSF-1 receptor (CSF-1R) in these kinds of carcinomas. ConclusionWe speculated that MEOX2 could facilitate macrophage infiltration via CSF-1/CSF-1R signaling in ESCC and other kinds of digestive system carcinomas, which might serve as a novel target in prospective tumor immunotherapy.


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