High Level of METTL7B Indicates Poor Prognosis of Patients and Is Related to Immunity in Glioma

Glioma is the most common primary intracranial malignant tumor in adults. Although there have been many efforts on potential targeted therapy of glioma, the patient’s prognosis remains dismal. Methyltransferase Like 7B (METTL7B) has been found to affect the development of a variety of tumors. In this study, we collected RNA-seq data of glioma in CGGA and TCGA, analyzed them separately. Then, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, and receiver operating characteristic curve (ROC curve) analysis were used to evaluate the effect of METTL7B on prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) enrichment analyses were used to identify the function or pathway associated with METTL7B. Moreover, the ESTIMATE algorithm, Cibersort algorithm, Spearman correlation analysis, and TIMER database were used to explore the relationship between METTL7B and immunity. Finally, the role of METTL7B was explored in glioma cells. We found that METTL7B is highly expressed in glioma, and high expression of METTL7B in glioma is associated with poor prognosis. In addition, there were significant differences in immune scores and immune cell infiltration between the two groups with different expression levels of METTL7B. Moreover, METTL7B was also correlated with immune checkpoints. Knockdown of METTL7B revealed that METTL7B promoted the progression of glioma cells. The above results indicate that METTL7B affects the prognosis of patients and is related to tumor immunity, speculating that METTL7B may be a new immune-related target for the treatment of glioma.

Download Full-text

Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.780601 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ya Jun Liu ◽

Alphonse Houssou Hounye ◽

Zheng Wang ◽

Xiaowei Liu ◽

Jun Yi ◽

...

Keyword(s):

Risk Score ◽

Immune Cell ◽

Noncoding Rnas ◽

Enrichment Analysis ◽

Long Noncoding Rnas ◽

Gene Set Enrichment Analysis ◽

Risk Scores ◽

Roc Curve Analysis ◽

Good Reliability ◽

Normal Tissues

Cholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be valuable to elaborate autophagy-related lncRNAs (ARlncRNAs) in CCA, and indeed, there are still few studies concerning the role of ARlncRNAs in CCA. Here, a prognostic ARlncRNA signature was constructed to predict the survival outcome of CCA patients. Through identification, three differentially expressed ARlncRNAs (DEARlncRNAs), including CHRM3.AS2, MIR205HG, and LINC00661, were screened and were considered predictive signatures. Furthermore, the overall survival (OS) of patients with high-risk scores was significantly lower than that of patients with low scores. Interestingly, the risk score was an independent factor for the OS of patients with CCA. Moreover, receiver operating characteristic (ROC) curve analysis showed that the screened and constructed prognosis signature for 1 year (AUC = 0.884), 3 years (AUC =0.759), and 5 years (AUC = 0.788) presented a high score of accuracy in predicting OS of CCA patients. Gene set enrichment analysis (GSEA) revealed that the three DEARlncRNAs were significantly enriched in CCA-related signaling pathways, including “pathways of basal cell carcinoma”, “glycerolipid metabolism”, etc. Quantitative real-time PCR (qRT-PCR) showed that expressions of CHRM3.AS2, MIR205HG, and LINC00661 were higher in CCA tissues than those in normal tissues, similar to the trends detected in the CCA dataset. Furthermore, Pearson’s analysis reported an intimate correlation of the risk score with immune cell infiltration, indicating a predictive value of the signature for the efficacy of immunotherapy. In addition, the screened lncRNAs were found to have the ability to modulate the expression of mRNAs by interacting with miRNAs based on the established lncRNA-miRNA-mRNA network. In conclusion, our study develops a novel nomogram with good reliability and accuracy to predict the OS of CCA patients, providing a significant guiding value for developing tailored therapy for CCA patients.

Download Full-text

Comprehensive Analysis of a ceRNA Network Identifies lncR-C3orf35 Associated with Poor Prognosis in Osteosarcoma

BioMed Research International ◽

10.1155/2020/3178037 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yi Shi ◽

Jianhua Ren ◽

Ze Zhuang ◽

Wenhui Zhang ◽

Zhe Wang ◽

...

Keyword(s):

Poor Prognosis ◽

Immune Cell ◽

Bone Cancer ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Regulatory Mechanisms ◽

Messenger Rnas ◽

Cerna Network ◽

Potential Biomarker ◽

Hmgb1 Expression

Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

Download Full-text

Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer: An Integrated Bioinformatics Analysis

10.21203/rs.3.rs-33369/v1 ◽

2020 ◽

Author(s):

Qiaoyun Zhao ◽

Rulin Zhao ◽

Conghua Song ◽

Huan Wang ◽

Jianfang Rong ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Poor Prognosis ◽

Bioinformatics Analysis ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Biological Processes ◽

Coexpressed Genes

Abstract Background Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis.Methods IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database.Results IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the IGFBP7 expression level was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs).Conclusions We demonstrate that increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC. IGFBP7 might be a potential biomarker for the diagnosis and targeted therapy for GC.

Download Full-text

Low UGP2 Expression Is Associated with Tumour Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2020/3231273 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Qiuyue Hu ◽

Shen Shen ◽

Jianhao Li ◽

Liwen Liu ◽

Xin Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Cox Regression ◽

Tumour Progression ◽

Enrichment Analysis ◽

Malignant Tumour ◽

Diagnostic Value ◽

Gene Set Enrichment Analysis ◽

Uridine Diphosphate ◽

Roc Curve Analysis

Hepatocellular carcinoma (HCC) is a malignant tumour associated with a high mortality rate and poor prognosis worldwide. Uridine diphosphate-glucose pyrophosphorylase 2 (UGP2), a key enzyme in glycogen biosynthesis, has been reported to be associated with the occurrence and development of various cancer types. However, its diagnostic value and prognostic value in HCC remain unclear. The present study observed that UGP2 expression was significantly downregulated at both the mRNA and protein levels in HCC tissues. Receiver operating characteristic (ROC) curve analysis revealed that UGP2 may be an indicator for the diagnosis of HCC. In addition, Kaplan-Meier and Cox regression multivariate analyses indicated that UGP2 is an independent prognostic factor of overall survival (OS) in patients with HCC. Furthermore, gene set enrichment analysis (GSEA) suggested that gene sets negatively correlated with the survival of HCC patients were enriched in the group with low UGP2 expression levels. More importantly, a significant correlation was identified between low UGP2 expression and fatty acid metabolism. In summary, the present study demonstrates that UGP2 may contribute to the progression of HCC, indicating a potential therapeutic target for HCC patients.

Download Full-text

A Novel Prognostic Biomarker of Luminal Breast Cancer: High CD39 Expression Is Related to Poor Survival

Frontiers in Genetics ◽

10.3389/fgene.2021.682503 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaojian Ni ◽

Wenze Wan ◽

Jingjing Ma ◽

Xinyou Liu ◽

Bohao Zheng ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cell ◽

Statistical Tests ◽

Characteristic Curve ◽

Multivariable Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Luminal Breast Cancer ◽

Functional Surface

BackgroundCD39 is one of the functional surface markers for T regulatory cells, the prognostic role and immune-related effects of CD39 in luminal breast cancer (BC) patients has not been evaluated yet. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal BC patients.MethodsClinical information and RNA-sequencing (RNA-Seq) expression data were extracted from The Cancer Genome Atlas (TCGA). Patients were divided into a high or low CD39 expression group by the optimal cutoff value (4.18) identified from the receiver operating characteristic curve analysis. The relationships between CD39 expression and clinic pathological features were evaluated by the corresponding statistical tests. Survival analyses were applied to evaluate the overall survival between the high and low CD39 expression groups in luminal BC. Furthermore, Gene Expression Omnibus datasets were used for external data validation. Gene set enrichment analysis (GSEA) was also performed, and CIBERSORT was used to analyze the immune cell populations.ResultsAnalysis of 439 cases of tumor data showed that CD39 was overexpressed in luminal BC. The multivariable analysis suggested that CD39 expression was an independent prognostic factor for luminal BC patients. GSEA suggested that CD39 might play an important role in luminal BC progression through immune regulation. Analysis of immune cell patterns revealed high CD39 expression correlated to a higher proportion of CD8+ T cells and M2 macrophages.ConclusionThis study demonstrates that CD39 expression correlates with the prognosis of luminal BC through TCGA database mining. Further studies are warranted further to elucidate this potential novel therapeutic strategy for BC.

Download Full-text

Prognostic Significance of mRNA Expression RBBP8 or its Methylation in Gliomas

10.21203/rs.3.rs-713313/v1 ◽

2021 ◽

Author(s):

Zhengdong Liu ◽

Xingbo Cheng ◽

Yanzheng Gao ◽

Zhibin Han ◽

Shaochong Lin ◽

...

Keyword(s):

Poor Prognosis ◽

Immune Cell ◽

Cox Regression ◽

Prognostic Significance ◽

Gene Set Enrichment Analysis ◽

Immune Checkpoints ◽

Low Grade ◽

Risk Indicator ◽

Carcinogenic Effect ◽

Who Grade

Abstract Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan–Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. A meta-analysis confirmed the carcinogenic effect of RBBP8 on glioma, while the Tumor Immune Estimation Resource analysis showed that RBBP8 was positively correlated with the infiltration of six immune cell types in low-grade glioma, but only with dendritic cells in glioblastoma multiforme. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 can promote the activation of cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.

Download Full-text

A Risk Signature Established From Three Coagulation-fibrinolysis Genes Predicts Prognosis in Digestive System Pancancer

10.21203/rs.3.rs-1157925/v1 ◽

2022 ◽

Author(s):

Xingyun Wang ◽

Jinli Ji ◽

Ying Jiang ◽

Yiyang Zhao ◽

Zheyao Song ◽

...

Keyword(s):

High Risk ◽

Poor Prognosis ◽

Digestive System ◽

Risk Group ◽

Epigenetic Modification ◽

Enrichment Analysis ◽

Risk Groups ◽

High Risk Group ◽

Gene Set Enrichment Analysis ◽

Cox Analysis

Abstract Venous thromboembolism (VTE) is one of the major complications of digestive system cancer, and coagulation-fibrinolysis genes play an important role in VTE. We used univariate Cox analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis to construct 3-PCFGs (prognostic coagulation-fibrinolysis genes) model based on six prognostic coagulation-fibrinolysis genes. Gene set enrichment analysis (GSEA) was used to analyze the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the high- and low-risk groups. In addition, we classified digestive system pancancer patients into three clusters A, B, and C based on 3-PCFGs by K means. High-risk group and cluster C were associated with poor prognosis in digestive system pancancer. The m6A-related genes ALKBH5, FTO, RBM15, YTHDC1, and YTHDC2 (P<0.001) were highly expressed in the high-risk group and cluster C. The risk score was positively correlated with cancer-associated fibroblasts and endothelial cells. Cluster C had the highest immune score and stromal score. The poor prognosis in the high-risk group and cluster C may be affected by m6A epigenetic modification and immune microenvironment components in the digestive system pancancer.

Download Full-text

A Novel Ferroptosis-Related lncRNA Signature and an Immune Perspective of Cervical Cancer

10.21203/rs.3.rs-900510/v1 ◽

2021 ◽

Author(s):

Pengxiang Li ◽

Dongchun Qin ◽

Xuefeng Lv ◽

Lu Liu ◽

Mengle Peng

Keyword(s):

Cervical Cancer ◽

Cox Regression ◽

Enrichment Analysis ◽

Risk Groups ◽

Gene Expression Omnibus ◽

Gene Set Enrichment Analysis ◽

Immune Checkpoints ◽

Roc Curve Analysis ◽

Cox Regression Analysis ◽

Immune Related Genes

Abstract Background: Cervical cancer (CC) is the most common reproductive neoplasm in women, especially in developing countries. Ferroptosis, a novel type of cell death, and lncRNAs play critical roles in the prognosis of CC patients and antitumor immunity. Methods: A ferroptosis-related lncRNA signature (FRLS) was constructed by LASSO Cox regression analysis. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, multivariate analysis, and nomogram were used to evaluate and predict the FRLS. Based on the FRLS, immune-related genes, the tumor microenvironment (TME), immune checkpoints, and immunotherapy were investigated. Results: The FRLS was composed of ten lncRNAs and was markedly associated with the overall survival (OS) of CC patients. Gene set enrichment analysis (GSEA) demonstrated that the FRLS was largely associated with immune-related pathways. Weighted gene co-expression network analysis (WGCNA) was performed to analyze immune-related genes and to identify the optimal modules and genes. TLR4 was eventually identified, and its expression was verified in the Gene Expression Omnibus (GEO) database. Then, quantitative real-time PCR (qRT-PCR) was used to validate the results in CC and paracancerous tissues. Besides, our results showed that CD8+ T cells were significantly correlated between the low- and high-risk groups, and it could modulate ferroptosis during tumor immunotherapy. The expression of immune checkpoints was substantially different between the two groups. Additionally, tumor immune dysfunction and exclusion (TIDE) was applied to predict the sensitivity of immune checkpoint inhibitor (ICI) treatment. Conclusion: The FRLS established was significantly associated with prognosis; moreover, the FRLS is a prospective therapeutic target, and combined with immunotherapy, can be used in the treatment of CC patients.

Download Full-text

Elevated GAS2L3 Expression Correlates With Poor Prognosis in Patients With Glioma: A Study Based on Bioinformatics and Immunohistochemical Analysis

Frontiers in Genetics ◽

10.3389/fgene.2021.649270 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yan Zhou ◽

Limin Zhang ◽

Sirong Song ◽

Lixia Xu ◽

Yan Yan ◽

...

Keyword(s):

T Cell ◽

Immune Cell ◽

Enrichment Analysis ◽

Immunohistochemical Analysis ◽

Gene Set Enrichment Analysis ◽

Immune Checkpoints ◽

Gene Set Enrichment ◽

Bioinformatics Analyses ◽

Gene Set

BackgroundGrowth arrest–specific 2 like 3 (GAS2L3) is a cytoskeleton-associated protein that interacts with actin filaments and tubulin. Abnormal GAS2L3 expression has been reported to be associated with carcinogenesis. However, the biological role of GAS2L3 in glioma remains to be determined.MethodsThe transcriptome level of GAS2L3 and its relationship with clinicopathological characteristics were analyzed among multiple public databases and clinical specimens. Bioinformatics analyses were conducted to explore biological functions and prognostic value of GAS2L3 in glioma.ResultsGAS2L3 was substantially expressed in glioma, and high GAS2L3 expression correlated with shorter overall survival time and poor clinical variables. Gene set enrichment analysis (GSEA), single-sample gene-set enrichment analysis, and CIBERSORT algorithm analyses showed that GAS2L3 expression was closely linked to immune-related pathways, inflammatory activities, and immune cell infiltration. Moreover, GAS2L3 was synergistic with T cell–inflamed gene signature, immune checkpoints, T-cell receptor diversities, and neoantigen numbers.ConclusionThis study suggests that GAS2L3 is a prognostic biomarker for glioma, providing a reference for further study of the potential role of GAS2L3 in the immunomodulation of glioma.

Download Full-text

ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

Scientific Reports ◽

10.1038/s41598-021-90330-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yangming Hou ◽

Yingjuan Xu ◽

Dequan Wu

Keyword(s):

Gastric Cancer ◽

Tumor Microenvironment ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Tumor Promoter ◽

Protein Protein Interaction ◽

Oxidative Phosphorylation Pathway ◽

Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

Download Full-text