The Expression of Tripartite Motif Protein 36 and β-Catenin Correlates with the Prognosis of Esophageal Cancer

Aims. Tripartite motif protein 36 (TRIM36) plays a tumor-suppressive role in prostate cancer. However, there is little information on the clinical relevance of TRIM36 expression in esophageal cancer (ESCA). Methods. TRIM36 expression was analyzed by using The Cancer Genome Atlas (TCGA) ESCA dataset as well as by quantitative real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining on samples from our hospital. Results. In the current study, the analysis of TCGA ESCA dataset suggested the decreased expression of TRIM36 in ESCA tissues. Further analyses on samples from our hospital demonstrated that TRIM36 was significantly downregulated in ESCA tissues than in the noncancerous controls at both the mRNA and protein levels. Moreover, gene set enrichment analysis on TCGA ESCA dataset suggested that TRIM36 expression was inversely correlated with the β-catenin pathway. IHC staining data showed that 66.25% (53/80) and 51.25% (41/80) of ESCA cases had a low expression of TRIM36 and a high expression of β-catenin, respectively. By Fisher’s exact test, we found that TRIM36 protein expression was significantly correlated with tumor size (P=0.0104), tumor stage (P=0.0169), lymph node metastasis (P=0.0021), vital status (P=0.0443), and β-catenin expression (P=0.0329). These findings suggest the potential clinical significance of TRIM36 in ESCA. Kaplan–Meier and log-rank test demonstrated that a low expression of TRIM6 and a high expression of β-catenin were associated with poor overall survival of ESCA patients. Conclusions. Our study provides evidence for the prognostic value of TRIM36 in ESCA.

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Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma

BMC Medical Genetics ◽

10.1186/s12881-020-01066-2 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Erna Guo ◽

Haotang Wei ◽

Xiwen Liao ◽

Liuyu Wu ◽

Xiaoyun Zeng

Keyword(s):

Gene Family ◽

Colon Adenocarcinoma ◽

Enrichment Analysis ◽

Clinical Information ◽

Underlying Mechanism ◽

Tumor Stage ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Glutathione S Transferase ◽

Low Expression

Abstract Background Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown. Methods Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients. Results Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367–0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342–0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways. Conclusions In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.

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Downregulated ARID1A by miR-185 Is Associated With Poor Prognosis and Adverse Outcomes in Colon Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.679334 ◽

2021 ◽

Vol 11 ◽

Author(s):

Salem Baldi ◽

Hassan Khamgan ◽

Yuanyuan Qian ◽

Han Wu ◽

Zhenyu Zhang ◽

...

Keyword(s):

Cell Line ◽

Survival Curve ◽

Colon Adenocarcinoma ◽

Enrichment Analysis ◽

Adverse Outcomes ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Interaction Domain ◽

Molecular Features ◽

Low Expression

AT-rich interaction domain 1A (ARID1A) is a tumor suppressor gene that mutates in several cancer types, including breast cancer, ovarian cancer, and colorectal cancer (CRC). In colon adenocarcinoma (COAD), the low expression of ARID1A was reported but the molecular reason is unclear. We noticed that ARID1A low expression was associated with increased levels of miR-185 in the COAD. Therefore, this study aims to explore ncRNA-dependent mechanism that regulates ARID1A expression in COAD regarding miR-185. The expression of ARID1A was tested in COAD cell line under the effect of miR-185 mimics compared with inhibitor. The molecular features associated with loss of ARID1A and its association with tumor prognosis were analyzed using multi-platform data from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) to identify potential signaling pathways associated with ARID1A alterations in colon cancer. Kaplan-Meier survival curve showed that a low level of ARID1A was closely related to low survival rate in patients with COAD. Results showed that inhibiting miR-185 expression in the COAD cell line significantly restored the expression of ARID1A. Further, the increased expression of ARID1A significantly improved the prolonged overall survival of COAD. We noticed that there is a possible relationship between ARID1A high expression and tumor microenvironment infiltrating immune cells. Furthermore, the increase of ARID1A in tumor cells enhanced the response of inflammatory chemokines. In conclusion, this study demonstrates that ARID1A is a direct target of miR-185 in COAD that regulates the immune modulations in the microenvironment of COAD.

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Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.665192 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tian-Hao Li ◽

Cheng Qin ◽

Bang-Bo Zhao ◽

Hong-Tao Cao ◽

Xiao-Ying Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariate Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Wilcoxon Test ◽

Hepatic Tissue ◽

Gene Set Enrichment ◽

Poor Overall Survival ◽

Gene Set

Methyltransferase-like 18 (METTL18), a METTL family member, is abundant in hepatocellular carcinoma (HCC). Studies have indicated the METTL family could regulate the progress of diverse malignancies while the role of METTL18 in HCC remains unclear. Data of HCC patients were acquired from the cancer genome atlas (TCGA) and gene expression omnibus (GEO). The expression level of METTL18 in HCC patients was compared with normal liver tissues by Wilcoxon test. Then, the logistic analysis was used to estimate the correlation between METTL18 and clinicopathological factors. Besides, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore relevant functions and quantify the degree of immune infiltration for METTL18. Univariate and Multivariate Cox analyses and Kaplan–Meier analysis were used to estimate the association between METTL18 and prognosis. Besides, by cox multivariate analysis, a nomogram was conducted to forecast the influence of METTL18 on survival rates. METTL18-high was associated with Histologic grade, T stage, Pathologic stage, BMI, Adjacent hepatic tissue inflammation, AFP, Vascular invasion, and TP53 status (P < 0.05). HCC patients with METTL18-high had a poor Overall-Survival [OS; hazard ratio (HR): 1.87, P < 0.001), Disease-Specific Survival (DSS, HR: 1.76, P = 0.015), and Progression-Free Interval (PFI, HR: 1.51, P = 0.006). Multivariate analysis demonstrated that METTL18 was an independent factor for OS (HR: 2.093, P < 0.001), DSS (HR: 2.404, P = 0.015), and PFI (HR: 1.133, P = 0.006). Based on multivariate analysis, the calibration plots and C-indexes of nomograms showed an efficacious predictive effect for HCC patients. GSEA demonstrated that METTL18-high could activate G2M checkpoint, E2F targets, KRAS signaling pathway, and Mitotic Spindle. There was a positive association between the METTL18 and abundance of innate immunocytes (T helper 2 cells) and a negative relation to the abundance of adaptive immunocytes (Dendritic cells, Cytotoxic cells etc.). Finally, we uncovered knockdown of METTL18 significantly suppressed the proliferation, invasion, and migration of HCC cells in vitro. This research indicates that METTL18 could be a novel biomarker to evaluate HCC patients’ prognosis and an important regulator of immune responses in HCC.

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MYD88 Is a Potential Prognostic Gene and Immune Signature of Tumor Microenvironment for Gliomas

Frontiers in Oncology ◽

10.3389/fonc.2021.654388 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qinglong Guo ◽

Xing Xiao ◽

Jinsen Zhang

Keyword(s):

Tumor Microenvironment ◽

Cox Regression ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Who Grade ◽

Cox Regression Analysis ◽

Clinical Cases

PurposeTo explore the profiles of immune and stromal components of the tumor microenvironment (TME) and their related key genes in gliomas.MethodsWe applied bioinformatic techniques to identify the core gene that participated in the regulation of the TME of the gliomas. And immunohistochemistry staining was used to calculate the gene expressions in clinical cases.ResultsThe CIBERSORT and ESTIMATE were used to figure out the composition of TME in 698 glioma cases from The Cancer Genome Atlas (TCGA) database. Differential expression analysis identified 2103 genes between the high and the low-score group. Then the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, univariate Cox regression analysis, and protein–protein interaction (PPI) network construction were conducted based on these genes. MYD88 was identified as the key gene by the combination univariate Cox and PPI analysis. Furthermore, MYD88 expression was significantly associated with the overall survival and WHO grade of glioma patients. The genes in the high-expression MYD88 group were mainly in immune-related pathways in the Gene Set Enrichment Analysis (GSEA). We found that macrophage M2 accounted for the largest portion with an average of 27.6% in the glioma TIICs and was associated with high expression of MYD88. The results were verified in CGGA database and clinical cases in our hospital. Furthermore, we also found the MYD88 expression was higher in IDH1 wild types. The methylation rate was lower in high grade gliomas.ConclusionMYD88 had predictive prognostic value in glioma patients by influencing TIICs dysregulation especially the M2-type macrophages.

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Increased expression of homeobox 5 predicts poor prognosis: A potential therapeutic target for glioma

10.21203/rs.3.rs-376213/v1 ◽

2021 ◽

Author(s):

Chengran Xu ◽

Jinhai Huang ◽

Yi Yang ◽

Lun Li ◽

Guangyu Li

Keyword(s):

Cox Regression ◽

Homeobox Gene ◽

Enrichment Analysis ◽

Tissue Expression ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Who Grade ◽

Forecast Efficiency ◽

Genome Atlas

Abstract Background: The homeobox gene 5 (HOXB5) encodes a transcription factor that regulates the central nervous system embryonic development. Of note, its expression pattern and prognostic role in glioma remain unelucidated. This study aimed to identify the relationship between HOXB5 and glioma by investigating the HOXB5 expression data from the The Cancer Genome Atlas (TCGA) and The Genotype Tissue Expression (GTEx) databases and validating the obtained data using the Chinese Glioma Genome Atlas (CGGA) database. Kaplan-Meier and univariate cox regression analyses were performed to assess the prognostic value of HOXB5. The key functions and signaling pathways of HOXB5 were analyzed using GSEA and GSVA. Immune infiltration was calculated using Microenvironment Cell Populations-counter (MCP-counter), single-sample Gene Set Enrichment Analysis (ssGSEA), and ESTIMATE algorithms.Result: HOXB5 expression was elevated in glioma tissues. The increased levels of HOXB5 were significantly correlated with a higher WHO grade and aggressive cancer phenotypes. HOXB5 overexpression represented a risk factor that was associated with shorter overall survival (OS) while exhibiting a moderate forecast efficiency in most clinical subgroups. These results were validated using the CGGA and Rembrandt datasets. Furthermore, the functional analysis showed enrichment of angiogenesis, the IL6/JAK-STAT3 pathway, and inflammatory response in the tissues that showed high expression of HOXB5. Lastly, the high expression of HOXB5 was associated with enrichment of Tregs and MDSCs, and HOXB5 expression was shown to play a role in several immune checkpoint genes.Conclusions: HOXB5 may serve as a predictive factor of glioma malignancy and prognostic status and represents potential as a molecular treatment candidate.

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Upregulation of EMID1 accelerates to a favorable prognosis and immune infiltration in lung adenocarcinoma.

10.21203/rs.3.rs-28724/v1 ◽

2020 ◽

Author(s):

Chengrui Li ◽

Yufeng Wan ◽

Weijun Deng ◽

Fan Fei ◽

Linlin Wang ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Enrichment Analysis ◽

Notch Signaling Pathway ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Rank Test ◽

Survival Status ◽

Signed Rank Test

Abstract Background Lung cancer is a kind of refractory cancer. Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Although there are many ways to treat lung cancer, the survival rate of patients has not improved. Therefore, more new molecules need to be found for the diagnosis and treatment of LUAD. Methods The data from The Cancer Genome Atlas (TCGA) database were used to analyze the value of EMID1 in diagnosis and prognosis of LUAD. The relationship between clinic pathological features and EMID1 was analyzed with the Wilcoxon signed-rank test and logistic regression by R (v.3.5.1). Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential mechanism of EMID1 expression on the prognosis of LUAD. The correlation between tumor infiltrating immune cells and genes was assessed by CIBERSORT. In addition, GEPIA and Gene Expression Omnibus (GEO) database were used to verify the results. Results The decreased expression of EMID1 was significantly related to the late stage and metastasis of lung cancer. Kaplan Meier survival analysis showed that patients with low expression of EMID1 had worse prognosis than those with high expression of EMID1. Notch signaling pathway may be an important biological pathway for EMID1 to play a role in LUAD. In addition, CIBERSORT also found that the infiltration level of B cells was positively correlated with the expression of EMID1, which played an important role in the immune environment of LUAD. All results were validated in GEO and GEPIA database. Conclusion The analysis of EMID1 was helpful to understand the immune microenvironment of LUAD and improve the survival status of patients with LUAD. All the results suggested that EMID1 might be a new immune related prognostic marker of LUAD.

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High expression of PIMREG predicts poor survival outcomes and is correlated with immune infiltrates in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.11697 ◽

2021 ◽

Vol 9 ◽

pp. e11697

Author(s):

Feng Jiang ◽

Min Liang ◽

Xiaolu Huang ◽

Wenjing Shi ◽

Yumin Wang

Keyword(s):

Prognostic Value ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Gene Set Enrichment ◽

Gene Set ◽

Kaplan Meier ◽

Cancer Genome Atlas

Background PIMREG is upregulated in multiple cancer types. However, the potential role of PIMREG in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to explore its clinical significance in LUAD. Methods Using the Cancer Genome Atlas (TCGA) databases, we obtained 513 samples of LUAD and 59 normal samples from the Cancer Genome Atlas (TCGA) databases to analyze the relationship between PIMREG and LUAD. We used t and Chi-square tests to evaluate the level of expression of PIMREG and its clinical implication in LUAD. The prognostic value of PIMREG in LUAD was identified through the Kaplan–Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to screen biological pathways and analyze the correlation of the immune infiltrating level with the expression of PIMREG in LUAD. Results PIMREG was highly expressed in patients with LUAD. Specifically, the level of PIMREG gradually increased from pathological stage I to IV. Further, we validated the higher expression of PIMREG expressed in LUAD cell lines. Moreover, PIMREG had a high diagnostic value, with an -AUC of 0.955. Kaplan–Meier survival and Cox regression analyses revealed that the high expression of PIMREG was independently associated with poor clinical outcomes. In our prognostic nomogram, the expression of PIMREG implied a significant prognostic value. Gene set enrichment analysis (GSEA) identified that the high expression PIMREG phenotype was involved in the mitotic cell cycle, mRNA splicing, DNA repair, Rho GTPase signaling, TP53 transcriptional regulation, and translation pathways. Next, we also explored the correlation of PIMREG and tumor-immune interactions and found a negative correlation between PIMREG and the immune infiltrating level of T cells, macrophages, B cells, dendritic cells (DCs) , and CD8+ T cells in LUAD. Conclusions High levels of PIMREG correlated with poor prognosis and immune infiltrates in LUAD.

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ARID1A Upregulation Predicts Poor Survival in Patients with Liver Cancer

10.21203/rs.3.rs-166724/v1 ◽

2021 ◽

Author(s):

Feng Jiang ◽

Ke Wei ◽

Ming Wang ◽

Chuyan Wu

Keyword(s):

Overall Survival ◽

Liver Cancer ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Diagnosis And Prognosis ◽

Kaplan Meier ◽

Erbb Signaling

Abstract Objective: ARID1A has been identified as a possible biomarker for certain cancers. There is, however, some debate regarding its function in liver cancer. Methods: Associations between clinical variables and ARID1A were evaluated. Cox and Kaplan – Meier analysis were used to examine clinicalopathological factors linked to overall survival of patients with liver cancer. Gene Set Enrichment Analysis (GSEA) was conducted using the dataset of the Cancer Genome Atlas. Results: High expression of ARID1A was correlated with the gender and tumor topography (T) diagnosis of liver cancer. Patients with elevated ARID1A expression had poorer prognosis than those with low ARID1A expression. The study also showed that ARID1A was an independent risk factor for overall survival. GSEA established pathways involved in ERBB signaling, cancer, insulin signaling, mTOR signaling, MAPK signaling, VEGF signaling, Ubiquitin signaling, and Wnt signaling as differentially enriched in ARID1A-high expression liver cancer. Conclusion: ARID1A has been shown to be expressed at high rates of liver cancer and to represent a possible independent molecular marker for diagnosis and prognosis of liver cancer.

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ARID1A Upregulation Predicts Poor Survival in Patients With Liver Cancer

10.21203/rs.3.rs-146505/v1 ◽

2021 ◽

Author(s):

Feng Jiang ◽

Ke Wei ◽

Ming Wang ◽

Chuyan Wu

Keyword(s):

Overall Survival ◽

Liver Cancer ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Diagnosis And Prognosis ◽

Kaplan Meier ◽

Erbb Signaling

Abstract Objective: ARID1A has been identified as a possible biomarker for certain cancers. There is, however, some debate regarding its function in liver cancer. Methods: Associations between clinical variables and ARID1A were evaluated. Cox and Kaplan – Meier analysis were used to examine clinical pathological factors linked to overall survival of patients with liver cancer. Gene set enrichment analysis (GSEA) was conducted using the dataset of the cancer genome atlas(TCGA). Results: High expression of ARID1A was correlated with the gender and tumor topography (T) diagnosis of liver cancer. Patients with elevated ARID1A expression had poorer prognosis than those with low ARID1A expression. The study also showed that ARID1A was an independent risk factor for overall survival. GSEA established pathways involved in ERBB signaling, cancer, insulin signaling, mTOR signaling, MAPK signaling, VEGF signaling, Ubiquitin signaling, and Wnt signaling as differentially enriched in ARID1A-high expression liver cancer. Conclusion: ARID1A has been shown to be expressed at high rates of liver cancer and to represent a possible independent molecular marker for diagnosis and prognosis of liver cancer.

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Development of Multiscale Transcriptional Regulatory Network in Esophageal Cancer Based on Integrated Analysis

BioMed Research International ◽

10.1155/2020/5603958 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Zihao Xu ◽

Zilong Wu ◽

Jingtao Zhang ◽

Ruihao Zhou ◽

Jiane Wu ◽

...

Keyword(s):

Esophageal Cancer ◽

Transcriptional Regulatory Network ◽

Enrichment Analysis ◽

Diagnostic Value ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Integrated Analysis ◽

Rna Seq

Objective. To explore multiscale integrated analysis methods in identifying key regulators of esophageal cancer (ESCA). Methods. We downloaded the ESCA dataset from The Cancer Genome Atlas (TCGA) database, which contained RNA-seq data, miRNA-seq data, methylation data, and clinical phenotype information. Then, we combined ESCA-related genes from the NCBI-GENE and OMIM databases and RNA-seq dataset from TCGA to analyze differentially expressed genes (DEGs). Meanwhile, differentially expressed miRNAs (DEmiRNAs) and genes with differential methylation levels were identified. The pivot–module pairs were established using the RAID v2.0 database and TRRUST v2 database. Next, the multifactor-regulated functional network was constructed based on the above information. Additionally, gene corresponding targeted drug information was obtained from the DrugBank database. Moreover, we further screened regulators by assessing their diagnostic value and prognostic value, especially the value of distinguishing patients at TNM I stage from normal patients. In addition, the external database from the Gene Expression Omnibus (GEO) database was used for validation. Lastly, gene set enrichment analysis (GSEA) was performed to explore the potential biological functions of key regulators. Results. Our study indicated that CXCL8, CYP2C8, and E2F1 had excellent diagnostic and prognostic values, which may be potential regulators of ESCA. At the same time, the good early diagnosis ability of the three regulators also provided new insights for the diagnosis and early treatment of ESCA patients. Conclusion. We develop a multiscale integrated analysis and suggest that CXCL8, CYP2C8, and E2F1 are promising regulators with good diagnostic and prognostic values in ESCA.

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