scholarly journals Identification of ncRNA-Mediated Prognostic Value and Functions of MTHFD2 in Bladder Cancer

2021 ◽  
Author(s):  
Hao Zhang ◽  
Rui Li ◽  
Wanjun Deng ◽  
Jinfang Su ◽  
Huihua Xiong
Keyword(s):  
Bladder Cancer ◽  
Immune Cell ◽  
Tumor Development ◽  
Redox Balance ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Nucleic Acid Metabolism ◽  
Mitochondrial Enzymes ◽  
Immune Cell Infiltration ◽  
Cellular Mechanisms

Abstract Background: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), one of mitochondrial enzymes, is involved in folate and nucleic acid metabolism and maintains the cellular redox balance. However, the function of MTHFD2 in bladder cancer is still poorly characterized. This study was designed to elucidate the effect and regulatory mechanism of MTHFD2 on bladder cancer cells and explore the relationships between MTHFD2 and immune cell infiltration in tumor microenvironment (TME). Methods: The data from Oncomine, TIMER, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) database were extracted to evaluate the expression of MTHFD2 and its prognostic role in pan-cancer, especially in bladder cancer. Enrichment analyses, were utilized to explore the underlying cellular mechanisms. The ncRNA regulatory axis was established by Starbase database, and the PPI network was constructed by Cytoscape software. Ultimately, the relations between the expression of MTHFD2 and immune cell infiltration in bladder cancer was indicated by TCGA and TIMER databases.Results: Our results demonstrated that MTHFD2 expression was generally up-regulated in pan-cancers and its high expression was correlated with poor prognosis of patients with bladder cancer. Specifically, our study revealed that MTHFD2 was a powerful risk factor and involved in the tumor development of bladder cancer. Furthermore, hsa_circ_0046140 and hsa_circ_0006769/miR-383-5p/MTHFD2 axis could also play a significant role in tumorigenesis. Ultimately, a strong correlation was observed between MTHFD2 expression and various immune cell infiltration, which implied that MTHFD2 might serve as an agent in tumor immunotherapy. Conclusion: MTHFD2 is widely overexpressed in pan-cancers, and its expression is related with the prognosis of patients and the multiple immune cell infiltrates in TME. Besides, hsa_circ_0046140 and hsa_circ_0006769/miR-383-5p/MTHFD2 axis are implicated with the proliferation and invasion of tumors.

Identification of ncRNA-mediated prognostic Value and Immune Infiltration of MTHFD2 in Bladder Cancer

2021 ◽  
Author(s):  
Hao Zhang ◽  
Rui Li ◽  
Wanjun Deng ◽  
Huihua Xiong
Keyword(s):  
Bladder Cancer ◽  
Immune Cell ◽  
Tumor Development ◽  
Redox Balance ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Nucleic Acid Metabolism ◽  
Mitochondrial Enzymes ◽  
Immune Cell Infiltration ◽  
Cellular Mechanisms

Abstract Background: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), one of mitochondrial enzymes, is involved in folate and nucleic acid metabolism and maintains the cellular redox balance. However, the function of MTHFD2 in bladder cancer is still poorly characterized. This study was designed to elucidate the effect and regulatory mechanism of MTHFD2 on bladder cancer cells and explore the relationships between MTHFD2 and immune cell infiltration in tumor microenvironment (TME). Methods: The data from Oncomine, TIMER, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) database were extracted to evaluate the expression of MTHFD2 and its prognostic role in pan-cancer, especially in bladder cancer. Enrichment analyses, were utilized to explore the underlying cellular mechanisms. The ncRNA regulatory axis was established by Starbase database, and the PPI network was constructed by Cytoscape software. Ultimately, the relations between the expression of MTHFD2 and immune cell infiltration in bladder cancer was indicated by TCGA and TIMER databases.Results: Our results demonstrated that MTHFD2 expression was generally up-regulated in pan-cancers and its high expression was correlated with poor prognosis of patients with bladder cancer. Specifically, our study revealed that MTHFD2 was a powerful risk factor and involved in the tumor development of bladder cancer. Furthermore, hsa_circ_0046140 and hsa_circ_0006769/miR-383-5p/MTHFD2 axis could also play a significant role in tumorigenesis. Ultimately, a strong correlation was observed between MTHFD2 expression and various immune cell infiltration, which implied that MTHFD2 might serve as an agent in tumor immunotherapy. Conclusion: MTHFD2 is widely overexpressed in pan-cancers, and its expression is related with the prognosis of patients and the multiple immune cell infiltrates in TME. Besides, hsa_circ_0046140 and hsa_circ_0006769/miR-383-5p/MTHFD2 axis are implicated with the proliferation and invasion of tumors.

scholarly journals Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuomao Mo ◽  
Daiyuan Liu ◽  
Dade Rong ◽  
Shijun Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Immunosuppressive Microenvironment

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

scholarly journals SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shaokun Wang ◽  
Li Pang ◽  
Zuolong Liu ◽  
Xiangwei Meng
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
The Relationship

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

scholarly journals Prediction of Hepatocellular Carcinoma Prognosis and Immune Cell Infiltration Using Gene Signature Associated with Inflammatory Response

2022 ◽  
Vol 2022 ◽  
pp. 1-24
Author(s):  
Bin-Bin Da ◽  
Shuai Luo ◽  
Ming Huang ◽  
Fei Song ◽  
Rong Ding ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Inflammatory Response ◽  
Immune Cell ◽  
Cox Regression ◽  
Inflammatory Responses ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Differential Analysis

It has been demonstrated that the inflammatory response influences cancer development and can be used as a prognostic biomarker in various tumors. However, the relevance of genes associated with inflammatory responses in hepatocellular carcinoma (HCC) remains unknown. The Cancer Genome Atlas (TCGA) database was analyzed using weighted gene coexpression network analysis (WGCNA) and differential analysis to discover essential inflammatory response-related genes (IFRGs). Cox regression studies, both univariate and multivariate, were employed to develop a prognostic IFRGs signature. Additionally, Gene Set Enrichment Analysis (GSEA) was used to deduce the biological function of the IFRGs signature. Finally, we estimated immune cell infiltration using a single sample GSEA (ssGSEA) and x-cell. Our results revealed that, among the major HCC IFRGs, two (DNASE1L3 and KLKB1) were employed to create a predictive IFRG signature. The IFRG signature could correctly predict overall survival (O.S) as per Kaplan-Meier time-dependent roc curves analysis. It was also linked to pathological tumor stage and T stage and might be used as a prognostic predictor in HCC. GSEA analysis concluded that the IFRG signature might influence the immune response in HCC. Immunological cell infiltration and immune checkpoint molecule expression differed in the high-risk and low-risk groups. As a result of our findings, DNASILE may play a role in the tumor microenvironment. However, more research is necessary to confirm the role of DNASE1L3 and KLKB1.

scholarly journals An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sia Viborg Lindskrog ◽  
Frederik Prip ◽  
Philippe Lamy ◽  
Ann Taber ◽  
Clarice S. Groeneveld ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Chromosomal Instability ◽  
Prognostic Value ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Invasive Bladder Cancer ◽  
Immune Cell Infiltration ◽  
Muscle Invasive Bladder Cancer ◽  
Omics Analysis ◽  
Muscle Invasive

AbstractThe molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

scholarly journals Cancer Stemness Associated With Prognosis and the Efficacy of Immunotherapy in Adrenocortical Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoxi Shi ◽  
Yuanlin Liu ◽  
Shuai Cheng ◽  
Haidi Hu ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Potential Biomarker ◽  
Lower Expression

BackgroundCancer stem cells (CSCs) have been proven to influence drug resistance, recurrence, and metastasis in tumors. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in adrenocortical carcinoma.MethodsRNA-seq data and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA). The stemness indexes, mDNAsi and mRNAsi, were calculated to classify all samples into low-score and high-score groups. Two algorithms, based on the R language, ESTIMATE and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to assess the immune cell infiltration states of adrenocortical carcinoma patients. Weighted Gene Co-expression Network Analysis (WGCNA) was used to find genes that were related to the stemness of cancer. By bioinformatics methods, the correlations between biomarkers capable of predicting immune checkpoint inhibitors (ICIs) responses and stemness of cancer were explored.ResultsHigh-mRNAsi predicted shorter overall survival (OS) and a higher metastatic trend in adrenocortical carcinoma (ACC) patients. Compared with the low-mRNAsi group, the high-mRNAsi group had a lower ImmuneScore and StromalScroe. Twenty-two stemness-related prognostic genes were obtained by WGCNA, which focused on the function of the cell cycle and cell mitosis. Immune cell infiltration, especially CD8+T cell, increased in the low-mRNAsi group compared with the high-mRNAsi group. Lower expression of PD-L1, CTLA-4, and TIGHT was evaluated in the high-mRNAsi group.ConclusionsACC patients with high-mRNAsi have poor prognosis and less immune cell infiltration. Combined with the finding of lower expression of CTLA-4, TIGHT, and PD-L1 in the high-mRNAsi group, we came to the conclusion that stemness index is a potential biomarker to predict the effectiveness of ICIs.

scholarly journals Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanghui Zhao ◽  
Junhua An ◽  
Qian Pu ◽  
Wenwen Geng ◽  
Haiyun Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Clinical Samples ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients ◽  
Gene Signatures ◽  
Immune Phenotypes ◽  
Processing Stability

The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this study, we comprehensively evaluated the genetic variations and transcript expressions of 15 m6A regulators in 1,079 breast cancer samples from the Cancer Genome Atlas (TCGA) database. We validated major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal tissues from 39 pairs of clinical breast cancer samples with different molecular subtypes, and especially high expression of m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A regulators’ pattern showed distinct overall survival, immune activation status, and immune cell infiltration, and clinical samples confirmed the diversity of lymphocytic infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes, it suggested that m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m6A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy.

scholarly journals Landscape of Immune Cell Infiltration in Cervical Cancer

2021 ◽  
Author(s):  
Shasha Shi ◽  
Fu Peng ◽  
Chenghao Yu
Keyword(s):  
Cervical Cancer ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Cancer Tissues

Abstract BackgroundCervical cancer is a life-threatening cancer among women. It is the second most prevalent malignant tumor in women. It ranks high in cancer deaths among women worldwide, including in the United States. Immune checkpoint inhibitors have emerged as an important therapeutic approach to treat several cancers, including cervical cancer. Notably, the development and progress of cervical cancer may be related to sustained immune response. This underlines the need to clarify immune cell infiltration (ICI) in cervical cancer tissues. MethodsIn this study, disease-related information of 964 cervical cancer patients was first retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We utilized bioinformatics data to analyze the expression profiles of immune genes in cervical cancer tissues. ResultsPatients were divided into high and low groups according to ICI score. High ICI scores corresponded with activation of immune signaling pathways and high tumor mutation burden (TMB), which was related to better prognosis of G1-2 cervical cancer. In addition, most immune checkpoints and immuno-related genes such as CD274, CD8A, CXCL10, etc. were over-expressed in the high ICI group. ConclusionsThis study demonstrated that ICI score can accurately predict the prognosis of cervical cancer. Understanding ICI patterns will deepen our understanding of tumor microenvironment (TME) of cervical cancer, which may create the foundation for the development of efficient immunotherapeutic strategies against the cancer.

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