scholarly journals Construction and Validation of an Immune-Related Gene Prognostic Index for Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Qinghua Ji ◽  
Yingying Cai ◽  
Sachin Mulmi Shrestha ◽  
Duo Shen ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Index ◽  
Enrichment Analysis ◽  
Response To Therapy ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Immune Related Gene

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.

scholarly journals Identifying the p65-Dependent Effect of Sulforaphene on Esophageal Squamous Cell Carcinoma Progression via Bioinformatics Analysis

2020 ◽  
Vol 22 (1) ◽  
pp. 60
Author(s):  
Sichong Han ◽  
Zhe Wang ◽  
Jining Liu ◽  
Qipeng Yuan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Dependent Manner

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.

scholarly journals MEOX2 Serves as a Novel Biomarker Associated with Macrophage Infiltration in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
zhen wang ◽  
han yang ◽  
rusi zhang ◽  
bin luo ◽  
bingchen xu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Digestive System ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Macrophage Infiltration ◽  
High Morbidity

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.

scholarly journals A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guichuan Huang ◽  
Jing Zhang ◽  
Ling Gong ◽  
Yi Huang ◽  
Daishun Liu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Cox Regression ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Cox Regression Analysis

Abstract Background Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. Conclusion A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

scholarly journals Identification of tumor-infiltrating lymphocyte subpopulations correlated with patient prognosis in esophageal squamous cell carcinoma

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110162
Author(s):  
Lin Peng ◽  
Wenwu He ◽  
Feng Ye ◽  
Yane Song ◽  
Xinying Shi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Suppressor Cells ◽  
Enrichment Analysis ◽  
Postoperative Chemotherapy ◽  
Th2 Cells

Objective To identify biomarkers related to esophageal squamous cell carcinoma (ESCC) prognosis by analyzing genetic variations and the infiltration levels of tumor-infiltrating lymphocytes (TILs) in patients. Methods The clinical features of 61 patients with ESCC were collected. DNA panel sequencing was performed to screen differentially expressed genes (DEGs). Transcriptome sequencing was performed to identify gene expression profiles, and subsequent enrichment analysis of DEGs was conducted using Metascape. Results We identified 488 DEGs between patients with ESCC with distinct prognoses that were mainly enriched in the human immune response, fibrinogen complex, and protein activation cascade pathways. Among patients with ESCC treated with postoperative chemotherapy, those with a high infiltration level of myeloid-derived suppressor cells (MDSCs) had longer overall survival (OS), and OS was positively correlated with the infiltration level of T helper type 2 (Th2) cells among patients treated without chemotherapy after surgery. Additionally, in the case of MDSCs >0.7059 or Th2 cells <0.6290, patients receiving postoperative chemotherapy had a longer OS than those treated without chemotherapy following surgery. Conclusion The level of MDSCs or Th2 cells can be used as a biomarker for assessing the prognosis of patients with ESCC treated with or without postoperative chemotherapy, respectively.

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