scholarly journals JAK3 and TYK2 Serve as Prognostic Biomarkers and Are Associated with Immune Infiltration in Stomach Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lingkai Meng ◽  
Ling Ding ◽  
Yue Yu ◽  
Wang Li ◽  
Tao Huang
Keyword(s):  
Signaling Pathway ◽  
Malignant Tumors ◽  
Adaptive Immune Response ◽  
Tumor Grade ◽  
Nodal Metastasis ◽  
Prognostic Biomarkers ◽  
Poor Overall Survival ◽  
Immune Infiltration ◽  
Chemokine Signaling ◽  
Stomach Adenocarcinoma

Background. Stomach adenocarcinoma (STAD) is one of the most common malignant tumors. The Janus kinases (JAKs) play a significant part in cellular biological process, inflammation, and immunity. The roles of JAKs in STAD are still not systematically described. Methods. A series of bioinformatics tools were used to clarify the role of JAKs in STAD. Results. JAK3/TYK2 levels were significantly increased in STAD during subgroup analyses based on gender, tumor grade, cancer stages, and nodal metastasis status. STAD patients with high levels of JAK3/TYK2 had poor overall survival, postprogression survival, and first progression. Immune infiltration revealed a significant correlation between JAK3/TYK2 expression and the abundance of immune cells as well as immune biomarker expression in STAD. JAK3/TYK2 was associated with the adaptive immune response, chemokine signaling pathway, and JAK-STAT signaling pathway. Conclusions. JAK3 and TYK2 serve as prognostic biomarkers and are associated with immune infiltration in STAD.

scholarly journals Identification of Hub Genes and Immune Infiltration in Psoriasis by Bioinformatics Method

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxing Su ◽  
Yuqian Wei ◽  
Biao Huang ◽  
Jiang Ji
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nk Cells ◽  
Signaling Pathway ◽  
Control Sample ◽  
Gene Expression Omnibus ◽  
Ppi Network ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Chemokine Signaling

BackgroundPsoriasis is a chronic, prolonged, and recurrent skin inflammatory disease. However, the pathogenesis of psoriasis is not completely clear, thus we aimed to explore potential molecular basis of it.MethodsTwo datasets were downloaded from the Gene Expression Omnibus database. After identifying the differentially expressed genes of psoriasis skin lesion samples and healthy controls, three kinds of analyses, namely functional annotation, protein-protein interaction (PPI) network, and immune infiltration analyses, were performed.ResultsA total of 152 up-regulated genes and 38 down-regulated genes were selected for subsequent analyses. Evaluation of the PPI network identified the most important module containing 13 hub genes. Gene ontology analysis showed that the hub genes have a significant enrichment effect on positive regulation of cell migration, defense response to the other organism and epithelial cell differentiation. KEGG signaling pathway analysis showed that the hub genes were significantly enriched in chemokine signaling, Toll-like receptor signaling pathway, and IL-17 signaling pathway. Compared with the normal control sample, naive B cells, CD8+ T cells, activated memory CD4+ T cells, follicular helper T cells, gamma delta T cells, resting NK cells, monocytes, M0 macrophages, M1 macrophages, activated dendritic cells and neutrophils infiltrated more, while memory B cells, naive CD4+ T cells, regulatory T cells (Tregs), activated NK cells, resting mast cells, and eosinophils infiltrated less.ConclusionTo conclude, the hub genes and pathways identified from psoriasis lesions and normal controls along with the immune infiltration profile may provide new insights into the study of psoriasis.

scholarly journals Comprehensive Analysis of Hexokinase 2 Immune Infiltrates and m6A Related Genes in Human Esophageal Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Xu-Sheng Liu ◽  
Jia-Min Liu ◽  
Yi-Jia Chen ◽  
Fu-Yan Li ◽  
Rui-Min Wu ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Signaling Pathway ◽  
Tumor Grade ◽  
Gene Expression Omnibus ◽  
Vital Role ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cell Junction ◽  
Hexokinase 2 ◽  
Immune Infiltration

Background: Hexokinase 2 not only plays a role in physiological function of human normal tissues and organs, but also plays a vital role in the process of glycolysis of tumor cells. However, there are few comprehensive studies on HK2 in esophageal carcinoma (ESCA) needs further study.Methods: Oncomine, Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used to analyze the expression differences of HK2 in Pan-cancer and ESCA cohort, and to analyze the correlation between HK2 expression level and clinicopathological features of TCGA ESCA samples. GO/KEGG, GGI, and PPI analysis of HK2 was performed using R software, LinkedOmics, GeneMANIA and STRING online tools. The correlation between HK2 and ESCA immune infiltration was analyzed TIMER and TCGA ESCA cohort. The correlation between HK2 expression level and m6A modification of ESCA was analyzed by utilizing TCGA ESCA cohort.Results: HK2 is highly expressed in a variety of tumors, and its high expression level in ESCA is closely related to the weight, cancer stages, tumor histology and tumor grade of ESCA. The analysis results of GO/KEGG showed that HK2 was closely related to cell adhesion molecule binding, cell-cell junction, ameboidal-type cell migration, insulin signaling pathway, hif-1 signaling pathway, and insulin resistance. GGI showed that HK2 associated genes were mainly involved in the glycolytic pathway. PPI showed that HK2 was closely related to HK1, GPI, and HK3, all of which played an important role in tumor proliferation. The analysis results of TIMER and TCGA ESCA cohort indicated that the HK2 expression level was related to the infiltration of various immune cells. TCGA ESCA cohort analyze indicated that the HK2 expression level was correlated with m6A modification genes.Conclusion: HK2 is associated with tumor immune infiltration and m6A modification of ESCA, and can be used as a potential biological target for diagnosis and therapy of ESCA.

scholarly journals Prognostic Value and Immune Infiltrates of ABCA8 and FABP4 in Stomach Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ya Guo ◽  
Zhong Wei Wang ◽  
Wang Hui Su ◽  
Jing Chen ◽  
Ya Li Wang
Keyword(s):  
Poor Prognosis ◽  
Immune Cell ◽  
Genetic Alterations ◽  
Prognostic Biomarkers ◽  
Venn Diagram ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Interactive Analysis ◽  
Human Protein Atlas ◽  
Stomach Adenocarcinoma

Background. Stomach adenocarcinoma (STAD) is a common malignancy worldwide with poor prognosis. Therefore, it is important to identify a valuable prognostic biomarker for STAD. The aim of present study was to identify novel prognostic biomarkers for STAD and evaluate the potential role of hub genes in STAD. Methods. Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer RNA-Seq Nexus were performed to identify differentially expressed genes (DEGs). Subsequently, hub genes were selected by a Venn diagram, and the expression of key genes was confirmed by UALCAN database. Furthermore, survival analysis of these hub genes was performed using Oncolnc and Human Protein Atlas (HPA) database. Gene alteration status of hub genes was assessed by cBioPortal. Finally, we investigated the association between hub genes and immune cell infiltration in STAD through the Tumor Immune Estimation Resource (TIMER) and GEPIA database. Results. Three common hub genes were obtained, including 2 downregulated DEGs (ABCA8 and FABP4) and one upregulated DEG (SLC52A3). Furthermore, increased expression of ABCA8 and FABP4 and decreased expression of SLC52A3 were correlated with poor prognosis. Meanwhile, three hub genes showed genetic alterations in various datasets of STAD. Finally, our results showed that ABCA8 and FABP4 displayed a positive correlation with immune infiltration, especially in M2 macrophages. Conclusions. The results of this study suggest that ABCA8 and FABP4 may be used as prognostic biomarkers and correlated with immune infiltration in STAD.

scholarly journals Identification of long noncoding RNA RP11-89K21.1 and RP11-357H14.17 as prognostic signature of endometrial carcinoma via integrated bioinformatics analysis

2020 ◽  
Author(s):  
Lingling Gao ◽  
Xin Nie ◽  
Wenchao Zhang ◽  
Rui Gou ◽  
Yuexin Hu ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Growth Regulation ◽  
Malignant Tumors ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Biological Behavior ◽  
Receptor Protein ◽  
Immune Infiltration

Abstract Background: Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It’s meaningful to explore lncRNAs signature for providing prognostic value of EC. Methods：The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases. Results: We first identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.1), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including cytokine-mediated signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway and apoptotic signaling pathway. Moreover, RP11-89K21.1 and RP11-357H14.17 were correlated with immune infiltration including CD8_T cell, CD4_Tcell, Macrophage and Neutrophil. Conclusions: We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.

scholarly journals TSHZ3 is A Prognostic Biomarker with Immune Infiltration in Stomach Adenocarcinoma and Bladder Urothelial Carcinoma

2020 ◽  
Author(s):  
Xi Zhang ◽  
Ming Wang ◽  
Han-qi Lu ◽  
Qiu-xing He ◽  
Yan-ting You ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Prognostic Biomarker ◽  
Th2 Cells ◽  
Poor Overall Survival ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Bladder Urothelial Carcinoma ◽  
Stomach Adenocarcinoma

Abstract Background: This study aimed to investigate the expressions of Teashirt zinc finger homeobox 3 (TSHZ3) in different cancer types and identify the cancers of which prognosis can be predicted by TSHZ3 expression. Furthermore, we aimed to explore the correlations between tumor-infiltrating immune cells (TIICs) and TSHZ3 expression in these cancers.Methods: TSHZ3 expression was analyzed by the Oncomine database and Gene Expression Profiling Interactive Analysis (GEPIA). We examined the influence of TSHZ3 on the clinical prognosis with Kaplan-Meier plotter and TIMER (Tumor Immune Estimation Resource). The correlations between tumor immune infiltrates and TSHZ3 expressions were investigated with TIMER and validated by GEPIA.Results: TSHZ3 expressions were significantly higher in stomach adenocarcinoma (STAD) and bladder urothelial carcinoma (BLCA) when compared to normal tissues. Survival analysis results showed that high TSHZ3 expression was correlated with poor overall survival (OS) in STAD and BLCA. The infiltrations of pro-tumorigenic TIICs (M2 macrophages, monocytes, B cells and pDCs) were positively correlated with TSHZ3 expression in STAD and BLCA. Besides, the infiltration of other pro-tumorigenic TIICs (tumor-associated macrophages (TAMs), Th2 cells and Tregs) and expression of T cell exhaustion markers (PD-1 and TIM-3) were positively correlated with TSHZ3 expression in STAD.Conclusions: TSHZ3 expression was up-regulated in STAD and BLCA. High TSHZ3 expression predicted poor prognosis of patients with STAD or BLCA. In addition, TSHZ3 expression potentially contributes to the increased infiltrations of pro-tumorigenic TIICs. TSHZ3 can be used as a prognostic biomarker for predicting prognosis and immune infiltration in STAD and BLCA.

Identification of long noncoding RNA RP11-169F17.1 and RP11-669N7.2 as novel prognostic biomarkers of stomach adenocarcinoma based on integrated bioinformatics analysis

Epigenomics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1307-1321 ◽  
Author(s):  
Jue Yang ◽  
Hui Song
Keyword(s):  
Noncoding Rna ◽  
Disease Free Survival ◽  
Differentially Expressed ◽  
Prognostic Biomarkers ◽  
Gastric Diseases ◽  
Poor Overall Survival ◽  
Functional Roles ◽  
Cell Proliferation And Differentiation ◽  
Stomach Adenocarcinoma ◽  
H Pylori

Aim: We aim to identify differentially expressed long noncoding RNAs (lncRNAs) and explored their functional roles in stomach adenocarcinoma. Materials & methods: Based on public omics data, we identified disregulated lncRNAs and investigated their prognostic values and potential functions based on ceRNA hypothesis. Results: Among the 52 differentially expressed lncRNAs, upregulated RP11-169F17.1 and RP11-669N7.2 were significantly associated with both poor overall survival and disease-free survival. RP11-169F17.1 and RP11-669N7.2 strongly correlated with microRNAs in cancer, cell proliferation and differentiation. RP11-169F17.1 and RP11-669N7.2 closely related to Helicobacter pylori infection-induced gastritis, duodenal ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Conclusion: RP11-169F17.1 and RP11-669N7.2 act as novel prognostic biomarkers of stomach adenocarcinoma and may also play an important role in H. pylori infection-induced gastric diseases.

scholarly journals Knockdown of DIAPH3 Inhibits the Proliferation of Cervical Cancer Cells through Inactivating mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Linling Wan ◽  
Jiamin Zhu ◽  
Qunying Wu
Keyword(s):  
Cervical Cancer ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Poor Overall Survival ◽  
Western Blot Assay ◽  
Incidence And Mortality

Cervical cancer (CC) ranks fourth for both incidence and mortality among females in worldwide. Therefore, it is urgent to explore new therapeutic and diagnostic targets for cervical cancer. Diaphanous-related formin 3 (DIAPH3) has been identified to play crucial roles in many malignant tumors. But its function and potential mechanism in CC remain largely unknown. In our study, DIAPH3 was frequently upregulated in CC tissue samples and increased expression of DIAPH3 was associated with poor overall survival according to several databases. Through in vitro and in vivo experiments, we found that decreased expression levels of DIAPH3 significantly inhibited the progression of CC. The GSEA analysis and western blot assay indicated that DIAPH3 was associated with the mTOR signaling pathway. The univariate and multivariate Cox analysis indicated that DIAPH3 was an independent prognosis risk factor in TCGA-CESC. And we confirmed that DIAPH3 expression was clearly related to tumor immune infiltrating cells (TIICs) by the analysis of CIBERSORT and TIMER databases. Taken together, we revealed that DIAPH3 plays as an oncogene through mTOR signaling pathway and DIAPH3 might be a potential prognostic biomarker in CC.

scholarly journals Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

2020 ◽  
Author(s):  
Zhangya Pu ◽  
Yuanyuan Zhu ◽  
Xiaofang Wang ◽  
Yun Zhong ◽  
Fang Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Survival Analysis ◽  
Immune Cell ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Cerna Network

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC. Methods: RNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds. Results: The predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8 + T cells, CD4 + T cells, monocytes, macrophages, neutrophils, and dendritic cells. Conclusions: The findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

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