Comprehensive Analysis of Hexokinase 2 Immune Infiltrates and m6A Related Genes in Human Esophageal Carcinoma
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ABSTRACT:
SUBMITTER: Liu X
PROVIDER: S-EPMC8544599 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo identify the feature of N6-methyladenosine (m6A) methylation modification genes in acute aortic dissection (AAD) and explore their relationships with immune infiltration.MethodsThe GSE52093 dataset including gene expression data from patients with AAD and healthy controls was downloaded from Gene Expression Omnibus (GEO) database in order to obtain the differentially expressed genes (DEGs). The differentially methylated m6A genes were obtained from the GSE147027 dataset. The differentially expressed m6A-related genes were obtained based on the intersection results. Meanwhile, the protein-protein interaction (PPI) network of differentially expressed m6A-related genes was constructed, and hub genes with close relationships in the network were selected. Later, hub genes were verified by using the GSE153434 dataset. Thereafter, the relationships between these genes and immune cells infiltration were analyzed.ResultsA total of 279 differentially expressed m6A-related genes were identified in the GSE52093 and GSE147027 datasets. Among them, 94 genes were up-regulated in aortic dissection (AD), while the remaining 185 were down-regulated. As indicated by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, these genes were mainly associated with extracellular matrix (ECM) and smooth muscle cells (SMCs). The seven hub genes, namely, DDX17, CTGF, FLNA, SPP1, MYH11, ITGA5 and CACNA1C, were all confirmed as the potential biomarkers for AD. According to immune infiltration analysis, it was found that hub genes were related to some immune cells. For instance, DDX17, FLNA and MYH11 were correlated with Macrophages M2.ConclusionOur study identifies hub genes of AD that may serve as the potential biomarkers, illustrates of the molecular mechanism of AD, and provides support for subsequent research and treatment development.
| S-EPMC8967178 | biostudies-literature
Project description:Background: YTHDF1 is highly expressed in multiple tumors and affects tumor progression. However, there are only a few comprehensive studies on the analysis of YTHDF1 in esophageal cancer. Methods: We analyzed YTHDF1 expression in pan-cancer by comparing both the GEPIA and TCGA cohorts, and further verified the differences in YTHDF1 expression between the ESCA and normal groups by the GEO ESCA cohort and in vitro experiments. The correlation of YTHDF1 expression and the clinical characteristics of ESCA patients was analyzed using the TCGA ESCA clinical data. The GO and KEGG enrichment analyses of the YTHDF1 coexpressed genes were completed by bioinformatics analysis, and the GGI and PPI were constructed for the YTHDF1, respectively. The relationship between YTHDF1 expression and the infiltration of ESCA immune cells was analyzed by using the TIMER database and the TCGA ESCA cohort. The relationships between YTHDF1 expression levels and glycolysis and ferroptosis-related genes were analyzed using the TCGA and GEPIA ESCA cohorts. Finally, the ceRNA network that may be involved in YTHDF1 in ESCA was predicted and constructed through a variety of databases. Results: YTHDF1 was overexpressed in various cancers, and in vitro experiments confirmed that YTHDF1 expression was higher in ESCA samples than in normal samples. The expression of YTHDF1 has some accuracy in predicting the tumor outcome. Expression of YTHDF1 was significantly associated with multiple clinical features in ESCA patients. GO and KEGG enrichment analyses indicated that YTHDF1 coexpressed genes involved multiple biological functions. There is a potential association between YTHDF1 expression and multiple immune cell infiltration, glycolysis, and ferroptosis-related genes in ESCA. YTHDF1 may be involved in multiple ceRNA regulatory networks in ESCA, including PAXIP1-AS1/hsa-miR-376c-3p/YTHDF1 axis, THUMPD3-AS1/hsa-miR-655-3p/YTHDF1 axis, and SNHG20/hsa-miR-655-3p/YTHDF1 axis, respectively. Conclusion: YTHDF1 can serve as a biomarker of ESCA, related to the immune cell infiltration of ESCA, regulation of glycolysis and ferroptosis, and the ceRNA regulatory network.
| S-EPMC8983832 | biostudies-literature
Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common cancer types and represents a threat to global public health. N6-Methyladenosine (m6A) methylation plays a key role in the occurrence and development of many tumors, but there are still few studies investigating ESCC. This study attempts to construct a prognostic signature of ESCC based on m6A RNA methylation regulators and to explore the potential association of these regulators with the tumor immune microenvironment (TIME).MethodsThe transcriptome sequencing data and clinical information of 20 m6A RNA methylation regulators in 453 patients with ESCC (The Cancer Genome Atlas [TCGA] cohort, n = 95; Gene Expression Omnibus [GEO] cohort, n = 358) were obtained. The differing expression levels of m6A regulators between ESCC and normal tissue were evaluated. Based on the expression of these regulators, consensus clustering was performed to investigate different ESCC clusters. PD-L1 expression, immune score, immune cell infiltration and potential mechanisms among different clusters were examined. LASSO Cox regression analysis was utilized to obtain a prognostic signature based on m6A RNA methylation modulators. The relationship between the risk score based on the prognostic signature and the TIME of ESCC patients was studied in detail.ResultsSix m6A regulators (METTL3, WTAP, IGF2BP3, YTHDF1, HNRNPA2B1 and HNRNPC) were observed to be significantly highly expressed in ESCC tissues. Two molecular subtypes (clusters 1/2) were determined by consensus clustering of 20 m6A modulators. The expression level of PD-L1 in ESCC tissues increased significantly and was significantly negatively correlated with the expression levels of YTHDF2, METL14 and KIAA1429. The immune score, CD8 T cells, resting mast cells, and regulatory T cells (Tregs) in cluster 2 were significantly increased. Gene set enrichment analysis (GSEA) shows that this cluster involves multiple hallmark pathways. We constructed a five-gene prognostic signature based on m6A RNA methylation, and the risk score based on the prognostic signature was determined to be an independent prognostic indicator of ESCC. More importantly, the prognostic value of the prognostic signature was verified using another independent cohort. m6A regulators are related to TIME, and their copy-number alterations will dynamically affect the number of tumor-infiltrating immune cells.ConclusionOur study established a strong prognostic signature based on m6A RNA methylation regulators; this signature was able to accurately predict the prognosis of ESCC patients. The m6A methylation regulator may be a key mediator of PD-L1 expression and immune cell infiltration and may strongly affect the TIME of ESCC.
| S-EPMC8149800 | biostudies-literature
Project description:BackgroundGlucose transporter 1 (GLUT1) is encoded by the solute carrier family 2A1 (SLC2A1) gene and is one of the glucose transporters with the greatest affinity for glucose. Abnormal expression of GLUT1 is associated with a variety of cancers. However, the biological role of GLUT1 in esophageal carcinoma (ESCA) remains to be determined.MethodsWe analyzed the expression of GLUT1 in pan-cancer and ESCA as well as clinicopathological analysis through multiple databases. Use R and STRING to perform GO/KEGG function enrichment and PPI analysis for GLUT1 co-expression. TIMER and CIBERSORT were used to analyze the relationship between GLUT1 expression and immune infiltration in ESCA. The TCGA ESCA cohort was used to analyze the relationship between GLUT1 expression and m6A modification in ESCA, and to construct a regulatory network in line with the ceRNA hypothesis.ResultsGLUT1 is highly expressed in a variety of tumors including ESCA, and is closely related to histological types and histological grade. GO/KEGG functional enrichment analysis revealed that GLUT1 is closely related to structural constituent of cytoskeleton, intermediate filament binding, cell-cell adheres junction, epidermis development, and P53 signaling pathway. PPI shows that GLUT1 is closely related to TP53, GIPC1 and INS, and these three proteins all play an important role in tumor proliferation. CIBERSORT analysis showed that GLUT1 expression is related to the infiltration of multiple immune cells. When GLUT1 is highly expressed, the number of memory B cells decreases. ESCA cohort analysis found that GLUT1 expression was related to 7 m6A modifier genes. Six possible crRNA networks in ESCA were constructed by correlation analysis, and all these ceRNA networks contained GLUT1.ConclusionGLUT1 can be used as a biomarker for the diagnosis and treatment of ESCA, and is related to tumor immune infiltration, m6A modification and ceRNA network.
| S-EPMC8195627 | biostudies-literature
Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck malignant tumors. As the early symptoms of HNSCC are not obvious, and it is prone to recurrence and metastasis, making the overall survival (OS) rate of patients very low. Existing studies have shown m6A methylation plays a crucial role in various cancers, but it is rarely studied in HNSCC. This study aimed to explore the expression of m6A methylation-related genes in HNSCC and its correlation with prognosis, and to explore its relationship with immune infiltration.MethodsThe gene expression data of HNSCC patient tumor samples (tumor =510) and adjacent normal tissue samples (normal =50) were extracted from The Cancer Genome Atlas (TCGA) database, and the expression characteristics of m6A regulatory factors were described. Kaplan-Meier survival analysis was used to analyze the relationship between m6A regulatory factors and OS and disease-specific survival (DSS). Least absolute shrinkage and selection operator (LASSO) regression was used to construct the m6A regulatory factor-HNSCC risk prediction model. In addition, the relationship between m6A methylation-related genes and tumor immune infiltration were discussed.ResultsThe differential expression of 20 genes were identified by TCGA, and 18 genes (IGF2BP2, IGF2BP1, IGF2BP3, VIRMA, YTHDF1, YTHDF2, YTHDF3, ZC3H13, METTL14, ALKBH5, METTL3, RBMX, WTAP, YTHDC1, FTO, HNRNPC, HNRNPA2B1, and RBM15) were overexpressed in HNSCC. The survival rate of different gene expression levels was different. The high expression of YTHDC1 and YTHDC2 indicated better OS. Furthermore, for DSS, increased expression of YTHDC2 was also correlated with better clinical outcomes (P<0.05). At the same time, we drew a 3-gene risk score model in the TCGA-HNSCC cohort, and the survival curve showed compared with low-risk patients, high-risk patients had significantly worse OS (P<0.05). Gene enrichment analysis showed EPITHELIAL_MESENCHYMAL_TRANSITIO, MTORC1_SIGNALING, MYC_TARGETS_V1, MYC_TARGETS_V2, MYOGENESIS pathways, high TP53 mutations, and suppressive immunity were related to the high-risk group. The low-risk group was related to ALLOGRAFT_REJECTION, COMPLEMENT, IL6_JAK_STAT3_SIGNALING, INTERFERON_ALPHA_RESPONSE, INTERFERON_GAMMA_RESPONSE pathways, low TP53 mutations, and active immunity.ConclusionsThe m6A methyltransferase-related genes can predict the prognosis of HNSCC and are related to immune infiltration.
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Project description:According to the TIMER database, large tumor suppressor 2 (LATS2) is differentially expressed in various tumors. However, the correlation between LATS2 and esophageal squamous cell carcinoma (ESCC) and the association between LATS2 and immune infiltration in ESCC remain unclear. Our synthetic research on LATS2 in ESCC revealed that the expression was low in esophageal squamous epithelium tissues, revealing the pernicious and adverse prognosis of ESCC. The Kaplan-Meier survival investigation pointed out that low LATS2 expression would result in an adverse prognosis. Biological investigation indicated that LATS2 was engaged in cell migration, adhesion, and junction. To further explore the relationship between LATS2 and tumor immunity, we utilized CIBERSORT to assess immune infiltration. The findings revealed that specimens with lower LATS2 expression showed higher immune infiltration, including T-cell follicular helper cells, M0 macrophages, M1 macrophages, and myeloid dendritic cell resting. An association investigation indicated that LATS2 was negatively relevant to immune checkpoints that restrain operative antitumor immune reactions. We also conducted immunohistochemical staining to explore the link between LATS2 expression and immunophenotype. The indicated association between low LATS2 expression and an immunophenotype is conducive to our understanding of ESCC mini-environments and might offer new indications for enhancing new therapeutic targets.
| S-EPMC9479129 | biostudies-literature
Project description:BackgroundAs essential components of cycle growth, the cell division cycle-associated family genes (CDCAs) have crucial roles in tumor development and progression, especially in hepatocellular carcinoma (HCC). However, due to the tumor heterogeneity of HCC, little is known about the methylation variability of CDCAs in mediating phenotypic changes (e.g., immune infiltrates) in HCC. Presently, we aim to comprehensively explore the expression and prognosis of CDCAs methylation with regard to immune infiltrates of HCC.MethodsWe first identified the correlating differentially expressed genes (co-DEGs) among 19 different types of cancer cohorts (a total of 7,783 patients) and then constructed the weighted gene co-expressed and co-methylated networks. Applying the clustering analysis, significant modules of DEGs including CDCAs were selected and their functional bioinformatics analyses were performed. Besides, using DiseaseMeth and TIMER, the correlation between the methylation levels of CDCAs and tumor immune infiltrates was also analyzed. In final, to assess the influence of CDCAs methylation on clinical prognosis, Kaplan-Meier and Cox regression analysis were carried out.ResultA total of 473 co-DEGs are successfully identified, while seven genes of CDCAs (CDCA1-3 and CDCA5-8) have significant over-expression in HCC. Co-expressed and co-methylated networks reveal the strong positive correlations in mRNA expression and methylation levels of CDCAs. Besides, the biological enrichment analysis of CDCAs demonstrates that they are significantly related to the immune function regulation of infiltrating immune cells in HCC. Also, the methylation analysis of CDCAs depicts the strong association with the tumor immunogenicity, i.e., low-methylation of CDCA1, CDCA2, and CDCA8 dramatically reduced the immune infiltrate levels of T cells and cytotoxic lymphocytes. Additionally, CDCA1-6 and CDCA8 with low-methylation levels significantly deteriorate the overall survival of patients in HCC.ConclusionsThe co-expressed and co-methylated gene networks of CDCAs show a powerful association with immune function regulation. And the methylation levels of CDCAs suggesting the prognostic value and infiltrating immune differences could be a novel and predictive biomarker for the response of immunotherapy.
| S-EPMC7921702 | biostudies-literature
Project description:BackgroundN6A methylation (m6A) is a significant epigenetic modification that critically impacts post-transcriptional regulation and tumor occurrence and development. While previous studies have identified a role for epigenetic regulation in hepatocellular carcinoma (HCC), the potential function of the m6A cluster in Hepatitis B virus (HBV)-related HCC remains unclear.MethodsThe related information was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of 20 m6A regulators, we comprehensively evaluated the m6A clusters and systematically explored the correlation between these clusters and immune cell infiltration characteristics of the tumor microenvironment (TME). The patients were divided into low- and high-m6A score groups. Then, the immune cell infiltration, chemokines, and cytokines levels, and drug sensitivity were further explored between the two groups.ResultsThe m6A cluster predicted a better prognosis that was accompanied by increased immune cell infiltration. Using these results, an m6A score was established that could predict overall survival, immune checkpoints, and clinical treatments for patients with HBV-related HCC. This study demonstrated that m6A modifications affected tumorigenesis, TME, and the prognosis of patients with HBV-related HCC.ConclusionA comprehensive assessment of m6A patterns could improve the current understanding of immune cell infiltration patterns and inform the development of individualized cancer treatments.
| S-EPMC10385918 | biostudies-literature
Project description:The tumor microenvironment (TME) of esophageal squamous cell carcinoma (ESCC) impacts tumor progression but is poorly understood. We obtained tumor tissues from 279 patients after esophagectomy and characterized the TME in intraepithelial and stromal regions using multiplex fluorescent immunohistochemistry (mfIHC). A heterogeneous immune population infiltrating tumor and the uninvolved esophageal tissue were observed. The infiltration of intraepithelial programmed death ligand 1 (PD-L1)-positive tumor-associated macrophages (TAMs) and stromal granzyme B+ activated cytotoxic T cells (aCTLs) correlated with both prolonged overall survival (OS) and disease-free survival (DFS). The intraepithelial memory T cell infiltration predicted longer OS, while intraepithelial and stromal regulatory T cell (Treg) infiltration was associated with shortened OS and DFS, respectively. Multivariate models combining immune infiltrates and clinicopathological factors outperformed tumor-node-metastasis (TNM) stage in predicting OS and DFS at 3 and 5 years. The infiltration of Treg inversely correlated with that of the antitumor effectors including CTLs, aCTLs, and natural killer (NK) cells. Intraepithelial memory T cell infiltration also negatively correlated with PD-L1 expression. In spatial analysis, intraepithelial dendritic cell (DC)-memory T cell engagement increased in high PD-L1+ TAM infiltration group. The characterization of the TME revealed a complex interplay between immune populations and may be employed to stratify patient for prognosis prediction and immunotherapy.
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Project description:Glioblastoma (GBM), the most common and aggressive brain tumor, has a very poor outcome and high tumor recurrence rate. The immune system has positive interactions with the central nervous system. Despite many studies investigating immune prognostic factors, there is no effective model to identify predictive biomarkers for GBM. Genomic data and clinical characteristic information of patients with GBM were evaluated by Kaplan-Meier analysis and proportional hazard modeling. Deseq2 software was used for differential expression analysis. Immune-related genes from ImmPort Shared Data and the Cistrome Project were evaluated. The model performance was determined based on the area under the receiver operating characteristic (ROC) curve. CIBERSORT was used to assess the infiltration of immune cells. The results of differential expression analyses showed a significant difference in the expression levels of 2942 genes, comprising 1338 upregulated genes and 1604 downregulated genes (p < 0.05). A population of 24 immune-related genes that predicted GBM patient survival was identified. A risk score model established on the basis of the expressions of the 24 immune-related genes was used to evaluate a favorable outcome of GBM. Further validation using the ROC curve confirmed the model was an independent predictor of GBM (AUC = 0.869). In the GBM microenvironment, eosinophils, macrophages, activated NK cells, and follicular helper T cells were associated with prognostic risk. Our study confirmed the importance of immune-related genes and immune infiltrates in predicting GBM patient prognosis.
| S-EPMC7151008 | biostudies-literature