scholarly journals CXCL2/10/12/14 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma

2021 ◽  
Author(s):  
Tong Lin ◽  
E Zhang ◽  
Pei-pei Mai ◽  
Ying-zhao Zhang ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Cancer Immunity ◽  
Chemokine Ligands ◽  
Treatment Responses ◽  
Necrosis Factor

Background: C-x-C motif chemokine ligands (CXCLs) are critical regulators of cancer immunity and angiogenesis, which affect disease progression and treatment responses. The character of each CXCL in the prognosis and immune infiltration of HCC patients is unclear yet. Methods: Differentially expressed CXCLs between HCC and normal control were screened by Oncomine and GEPIA2. Genetic alternations of CXCLs in HCC were analyzed by cBioPortal. Clinicopathological relevance of CXCLs in HCC patients was analyzed using UALCAN. The prognostic value of CXCLs was evaluated using univariate and multivariate analyses. Correlations of CXCLs’ expression with immune infiltration, chemokines and their receptors were assessed integrating TIMER, TISIDB, and GEPIA2. The co-expressed genes of CXCLs were discovered, and functional enrichment analysis was performed for them. Results: CXCL9/10 was significantly higher expressed while CXCL2/12/14 was lower expressed in HCC than normal tissues, but they didn’t show significant clinicopathological relevance in HCC patients. High-expression of CXCL2/10/12/14 indicated favorable outcomes of HCC patients. The expression of CXCL9/10/12/14 was significantly positively correlated with the infiltration and biomarkers’ expression of various tumor-infiltrating immune cells, also the abundance of chemokines and their receptors. The co-expressed genes of the five CXCLs were extracellular components and regulated immune or inflammatory responses, and signaling pathways of chemokine, Toll-like receptor, tumor necrosis factor might be involved. Conclusion: This study proposed CXCL2/10/12/14 might predict outcomes of HCC patients and were extensively related with the immune microenvironment in HCC. It would be a prospective therapeutic strategy for HCC to enhance effective immunity surveillance through intervening in these CXCLs.

scholarly journals Transcriptome-Wide Map of N6-Methyladenosine Methylome Profiling in Human Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Aolin Li ◽  
Ying Gan ◽  
Congcong Cao ◽  
Binglei Ma ◽  
Quan Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Gene Expression Pattern ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Rna Modification ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Normal Tissues ◽  
Cancer Tissues

N6-Methyladenosine (m6A) is the most widespread internal RNA modification in several species. In spite of latest advances in researching the biological roles of m6A, its function in the development and progression of bladder cancer remains unclear. In this study, we used MeRIPty -55-seq and RNA-seq methods to obtain a comprehensive transcriptome-wide m6A profiling and gene expression pattern in bladder cancer and paired normal adjacent tissues. Our findings showed that there were 2,331 hypomethylated and 3,819 hypermethylated mRNAs, 32 hypomethylated and 105 hypermethylated lncRNAs, and 15 hypomethylated and 238 hypermethylated circRNAs in bladder cancer tissues compared to adjacent normal tissues. Furthermore, m6A is most often harbored in the coding sequence (CDS), with some near the start and stop codons between two groups. Functional enrichment analysis revealed that differentially methylated mRNAs, lncRNAs, and circRNAs were mostly enriched in transcriptional misregulation in cancer and TNF signaling pathway. We also found that different m6A methylation levels of gene might regulate its expression. In summary, our results for the first time provide an m6A landscape of human bladder cancer, which expand the understanding of m6A modifications and uncover the regulation of mRNAs, lncRNAs, and circRNAs through m6A modification in bladder cancer.

scholarly journals Identification of PKP 2/3 as potential biomarkers of ovarian cancer based on bioinformatics and experiments

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lingling Gao ◽  
Xiao Li ◽  
Qian Guo ◽  
Xin Nie ◽  
Yingying Hao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Biological Behavior ◽  
Cell Junction ◽  
Immune Infiltration ◽  
Potential Biomarker

Abstract Background Plakophilins (PKPs) are widely involved in gene transcription, translation, and signal transduction, playing a crucial role in tumorigenesis and progression. However, the function and potential mechanism of PKP1/2/3 in ovarian cancer (OC) remains unclear. It’s of great value to explore the expression and prognostic values of PKP1/2/3 and their potential mechanisms, immune infiltration in OC. Methods The expression levels, prognostic values and genetic variations of PKP1/2/3 in OC were explored by various bioinformatics tools and databases, and PKP2/3 were selected for further analyzing their regulation network and immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) enrichment were also conducted. Finally, the expression and prognosis of PKP2 were validated by immunohistochemistry. Results The expression level and prognosis of PKP1 showed little significance in ovarian cancer, and the expression of PKP2/3 mRNA and protein were upregulated in OC, showing significant correlations with poor prognosis of OC. Functional enrichment analysis showed that PKP2/3 and their correlated genes were significantly enriched in adaptive immune response, cytokine receptor activity, organization of cell–cell junction and extracellular matrix; KEGG analysis showed that PKP2/3 and their significantly correlated genes were involved in signaling pathways including cytokine-mediated signaling pathway, receptor signaling pathway and pathways in cancer. Moreover, PKP2/3 were correlated with lymphocytes and immunomodulators. We confirmed that high expression of PKP2 was significantly associated with advanced stage, poor differentiation and poor prognosis of OC patients. Conclusion Members of plakophilins family showed various degrees of abnormal expressions and prognostic values in ovarian cancer. PKP2/3 played crucial roles in tumorigenesis, aggressiveness, malignant biological behavior and immune infiltration of OC, and can be regarded as potential biomarker for early diagnosis and prognosis evaluation in OC.

scholarly journals Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema

2020 ◽  
Vol 11 ◽  
Author(s):  
Lokesh P. Tripathi ◽  
Mari N. Itoh ◽  
Yoshito Takeda ◽  
Kazuyuki Tsujino ◽  
Yasushi Kondo ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Integrative Approach ◽  
Chronic Obstructive ◽  
Lung Pathology ◽  
Obstructive Pulmonary Disease

While both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are multifactorial disorders characterized by distinct clinical and pathological features, their commonalities and differences have not been fully elucidated. We sought to investigate the preventive roles of tetraspanins Cd151 and Cd9 -that are involved in diverse cellular processes in lung pathophysiology- in pulmonary fibrosis and emphysema, respectively, and to obtain a deeper understanding of their underlying molecular mechanisms toward facilitating improved therapeutic outcomes. Using an integrative approach, we examined the transcriptomic changes in the lungs of Cd151- and Cd9-deficient mice using functional-enrichment-analysis, pathway-perturbation-analysis and protein-protein-interaction (PPI) network analysis. Circadian-rhythm, extracellular-matrix (ECM), cell-adhesion and inflammatory responses and associated factors were prominently influenced by Cd151-deletion. Conversely, cellular-junctions, focal-adhesion, vascular-remodeling, and TNF-signaling were deeply impacted by Cd9-deletion. We also highlighted a “common core” of factors and signaling cascades that underlie the functions of both Cd151 and Cd9 in lung pathology. Circadian dysregulation following Cd151-deletion seemingly facilitated progressive fibrotic lung phenotype. Conversely, TGF-β signaling attenuation and TNF-signaling activation emerged as potentially novel functionaries of Cd9-deletion-induced emphysema. Our findings offer promising avenues for developing novel therapeutic treatments for pulmonary fibrosis and emphysema.

scholarly journals SPP1 is a Prognostic Related Biomarker and Correlated With Tumor-Infiltrating Immune Cells in Ovarian Cancer

2021 ◽  
Author(s):  
Wen Gao ◽  
Sheng Yin ◽  
Haiyan Sun ◽  
Zhuyan Shao ◽  
Peipei Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Vital Role ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of some cancer types, but little is known whether it is a bystander or an actual player on driving immune infiltration in ovarian cancer.Methods: In this study, the expression of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and SPP1 immumohistochemical staining analysis was assessed by The HPA database. The clinical outcomes between SPP1 expression and ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were explored using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database.Results: SPP1 was found overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter OS and PFS survivals. Particularly, elevated SPP1 expression was significantly associated with stage III ovarian cancer. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in ovarian cancer. Of particular importance, functional enrichment analysis suggested that SPP1 strong related with immune response.Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer.Trial registration: Not applicable.

scholarly journals Construction of ceRNA Coexpression Network and Screening of Molecular Targets in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhao Hui ◽  
Wang Zhanwei ◽  
Yang Xi ◽  
Liu Jin ◽  
Zhuang Jing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Interactions ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Normal Tissues ◽  
Cerna Network ◽  
Cancer Tissues

Objective. To screen some RNAs that correlated with colorectal cancer (CRC). Methods. Differentially expressed miRNAs, lncRNAs, and mRNAs between cancer tissues and normal tissues in CRC were identified using data from the Gene Expression Omnibus (GEO) database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interactions (PPIs) were performed to do the functional enrichment analysis. And a lncRNA-miRNA-mRNA network was constructed which correlated with CRC. RNAs in this network were subjected to analyze the relationship with the patient prognosis. Results. A total of 688, 241, and 103 differentially expressed genes (diff-mRNA), diff-lncRNA, and diff-miRNA were obtained between cancer tissues and normal tissues. A total of 315 edges were obtained in the ceRNA network. lncRNA RP11-108K3.2 and mRNA ONECUT2 correlated with prognosis. Conclusion. The identified RNAs and constructed ceRNA network could provide great sources for the researches of therapy of the CRC. And the lncRNA RP11-108K3.2 and mRNA ONECUT2 may serve as a novel prognostic predictor of CRC.

scholarly journals Bioinformatics analysis of the differentially co-expressed genes and immune cell infiltration features associated with pulmonary arterial hypertension

2021 ◽  
Author(s):  
Wenshi Liu ◽  
Dongdong Zheng ◽  
Wenjing Lv ◽  
Ying Hua ◽  
Rong Huang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Integrin Subunit ◽  
Immune Cell Infiltration ◽  
Control Groups ◽  
Immune Infiltration ◽  
And Control

IntroductionThis study aimed to identify novel differentially co-expressed genes and to investigate the features of immune cell infiltration in PAH.Material and methodsThe GSE113439 and GSE117261 datasets were acquired from the Gene Expression Omnibus database. And the differentially expressed genes between PAH and control groups were identified based on the GSE117261 dataset. Weighted Gene Co-Expression Network Analysis (WGCNA) was adopted to analyze the pre-processed data. Functional enrichment analysis was then carried out to explore the biological functions of these genes modules. The differentially co-expressed key genes modules were in-depth verified by GEO2R analysis. The immune infiltration in PAH was investigated by Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT).ResultsWGCNA analysis found 15 differentially co-expressed genes modules, amongst which module blue indicated that it exhibited the strongest positive link to PAH, whereas module green presented the strongest negative association with PAH. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the genes in module blue were largely enriched in Lysosome, Complement, and coagulation cascades, and others, while the genes in module green were primarily enriched in the Chemokine signaling pathway, Platelet activation, etc. Integrin subunit alpha M (ITGAM) was identified as the differentially co-expressed key gene. Immune infiltration analysis by CIBERSORT showed that the differences between PAH and control groups or between PAH subgroups.ConclusionsITGAM was considered a promising biomarker to discriminate PAH from the control. Obvious differences were observed in immune infiltration between patients with PAH and normal groups.

scholarly journals SPP1 is a Prognostic Related Biomarker and Correlated with Tumor-Infiltrating Immune Cells in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Xiaofeng Wang ◽  
Kun Zhang ◽  
Li Geng ◽  
DongLi Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Tumor Promoter ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) functions as a tumor promoter in varies tumors, but little is known whether it is an actual player on driving immune infiltration in hepatocellular carcinoma. Methods: In this study, we identified the expression of SPP1 by Oncomine, GEPIA and TIMER databases, and assessed SPP1 immumohistochemical staining analysis by The HPA database. We evaluated the clinical outcomes between SPP1 expression and hepatocellular carcinoma patients via Kaplan-Meier Plotter. We also tested the relationship between SPP1 and critical oncogenes by TIMER and GEPIA databases. Then we explored immune infiltration analyses using TIMER and TISIDB datasets. In addition, we performed functional enrichment analyses with Metascape and GeneMANIA databases. Results: We found that SPP1 overexpressed in hepatocellular carcinoma tissues and high SPP1 expression was correlated with shorter OS and PFS survivals in hepatocellular carcinoma patients. SPP1 expression is positive correlation with critical oncogenes related stemness associated genes, cell cycle and proliferation, therapeutic resistance, metastasis, and tumor angiogenesis in hepatocellular carcinoma. Importantly, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in hepatocellular carcinoma. Notably, functional enrichment analysis suggested that SPP1 strong related with immune response. Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in hepatocellular carcinoma.

scholarly journals T-Box Transcription Factor 22 Is an Immune Microenvironment-Related Biomarker Associated With the BRAFV600E Mutation in Papillary Thyroid Carcinoma

2020 ◽  
Vol 8 ◽  
Author(s):  
Xubin Dong ◽  
Jingjing Song ◽  
Jing Hu ◽  
Cheng Zheng ◽  
Xiaohua Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
T Regulatory Cells ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Papillary Thyroid ◽  
Immune Microenvironment ◽  
Invasion And Migration ◽  
T Box ◽  
Normal Tissues

Papillary thyroid cancer (PTC) is the most common malignant disease in endocrine systems. T-box transcription factor 22 (TBX22) is a phylogenetically conserved family member that has not been widely characterized in cancers. In this study, we explored the potential clinical significance and biological functions of TBX22 in PTC. Comprehensive analyses of TBX22 were based on the public databases and our local qRT-PCR cohort. We observed that TBX22 was significantly downregulated in PTC compared with normal tissues. TBX22 was associated with several clinicopathological factors in PTC. Low TBX22 expression correlated with BRAFV600E and TERT mutation. Functional enrichment analysis revealed that cancer-related pathways and immune progress were closely associated with TBX22 in PTC. In TBX22-low PTC, high immune infiltration levels with increased CD8+ T cells, natural killer, M1 macrophages, and T-regulatory cells were observed. TBX22 was negatively correlated with the activity of different steps of the anticancer immunity cycle. Functionally, overexpression of TBX22 inhibited the proliferation, invasion, and migration in PTC cells, while knocking down of TBX22 showed the opposite effects. The present findings disclose that TBX22, as an immune microenvironment-related biomarker, could be an important tumor suppresser gene and might inform the management of PTC patients better.

scholarly journals LncRNA AC007255.1, an immune-related prognostic enhancer RNA in esophageal cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11698
Author(s):  
Qingqing Wang ◽  
Xiaoyan Yu ◽  
Ningning Yang ◽  
Lu Xu ◽  
Yunfeng Zhou
Keyword(s):  
Esophageal Cancer ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Rna Seq ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Enhancer Rna ◽  
Active Enhancer

Background Growing evidence has suggested that enhancer RNAs (eRNAs), a set of long non-coding RNAs (lncRNAs) that were derived from active enhancer regions, play critical roles in regulating gene expression in human cancers. Nevertheless potential functions of eRNAs in esophageal cancer ESCA have not yet been expounded. Here, this study aimed to explore key prognostic eRNAs in ESCA. Methods LncRNAs that were transcribed from active enhancer regions were analyzed utilizing the PreSTIGE algorithm, followed by prediction of their target genes. Based on the ESCA RNA-seq data from the TANRIC database, overall survival (OS)-related eRNAs were determined. The correlation between AC007255.1 expression and various clinical traits of ESCA was calculated. Functional enrichment analysis was presented based on its co-expressed genes. Based on the TIMER database, we analyzed correlations between AC007255.1 expression and immune infiltration levels. qRT-PCR was utilized to validate the expression of AC007255.1 and PRR15 in ESCA and normal tissues. Results Totally, 2,695 lncRNAs were transcribed from active enhancer regions. Among them, 33 were significantly related to OS. AC007255.1 was a key eRNA. PRR15 was a target gene of AC007255.1 (correlation coefficient r = 0.936). Patients with high AC007255.1 expression indicated poor OS time. There were significant correlations between AC007255.1 expression and clinical characteristics like pathological TNM, grade and stage. AC007255.1 was closely related to tight junction and neutrophil activation involved in immune response. Moreover, AC007255.1 expression was related to the infiltration levels of B cell, dendritic cell and neutrophil. qRT-PCR results confirmed that AC007255.1 and PRR15 were both up-regulated in ESCA tissues, and there was a positive correlation between the two. Conclusion Our findings identified a novel immune-related eRNA AC007255.1 in ESCA, which could be a promising prognostic factor for ESCA.

scholarly journals Identification Hub Genes of Consensus Molecular Subtype Correlation With Immune Infiltration and Predict Prognosis in Gastric Cancer

2021 ◽  
Author(s):  
Bin Yu ◽  
Xin Yu ◽  
Jianping Xiong ◽  
Mei Ma
Keyword(s):  
Gastric Cancer ◽  
Molecular Subtype ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
M2 Macrophage ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Potential Biomarkers

Abstract Gastric Cancer (GC) has a great fatality rate, meanwhile, there is still a lack of available biomarkers for prognosis. The goal of the research was to discover key and novel potential biomarkers for GC. We screened for the expression of significantly altered genes based on survival rates from two consensus molecular subtypes (CMS) of GC. Subsequently, functional enrichment analysis showed these genes involved in many cancers. And we picked 6 hub genes that could both secreted in the tumor microenvironment and expression enhanced in immune cells. Then, Kaplan Meier survival and expression detected in the tumor pathological stage were utilized to clarify the prognostic of these 6 hub genes. The results indicated that OGN, CHRDL2, C2orf40, THBS4, CHRDL1, and ANGPTL1, respectively, were significantly associated with poor OS in GC patients. And their expression increased with cancer advanced. Moreover, immune infiltration analysis displayed that those hub genes expression positively with M2 macrophage, CD8+ T Cell, most immune inhibitors, and majority immunostimulators. In summary, our results suggested that OGN, CHRDL2, C2orf40, THBS4, CHRDL1, and ANGPTL1 were all potential biomarkers for GC prognosis and might also be potential therapeutic targets for GC.

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