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

Author(s):  
Xu-Sheng Liu ◽  
Jia-Min Liu ◽  
Yi-Jia Chen ◽  
Fu-Yan Li ◽  
Rui-Min Wu ◽  
...  

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.

2021 ◽  
Author(s):  
Tianhao Li ◽  
Xiaohan Qin ◽  
Cheng Qin ◽  
Bangbo Zhao ◽  
Hongtao Cao ◽  
...  

Abstract Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis.Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD.Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P<0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro.Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxing Su ◽  
Yuqian Wei ◽  
Biao Huang ◽  
Jiang Ji

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.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lingling Gao ◽  
Xiao Li ◽  
Qian Guo ◽  
Xin Nie ◽  
Yingying Hao ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lingkai Meng ◽  
Ling Ding ◽  
Yue Yu ◽  
Wang Li ◽  
Tao Huang

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.


2020 ◽  
Author(s):  
Hao-ran Zheng ◽  
Ai-Min Jiang ◽  
Na Liu ◽  
Qian-Qian Ding ◽  
Fu-Mei Zhao ◽  
...  

Abstract Background: Several studies have investigated the relationship between secreted phosphoprotein 1 (SPP1) expression level and prognosis of various tumors, but the results are far from conclusive. Therefore, we performed the present meta-analysis to investigate the prognostic value of SPP1 in pan-cancer. Furthermore, a followed confirmation based on The Cancer Genome Atlas (TCGA) database was also performed to verify our results.Methods: We performed a systematic search from PubMed, Embase, Web of Science, and Cochrane Library databases and 19 articles, including 3403 patients and 9 types of tumors, were pooled in our meta-analysis. Overall survival (OS) and disease-free survival (DFS), which correlated with SPP1 expression, were considered as the primary outcome. Subgroup analyses, sensitivity analysis, and publication bias were used to investigate heterogeneity and reliability of the results. Furthermore, we also explored the relationship between SPP1 expression and clinical parameters of tumor patients. Finally, the results were verified with TCGA database and we further explored the relationship between SPP1 expression and tumor immuno-microenvironment (TIME), DNA methylation, and enriched gene pathway.Results: Our meta-analysis showed that high-expressed SPP1 was significantly related to poor OS and DFS in various cancers, especially in liver hepatocellular carcinoma (LIHC). Furthermore, we also identified that the high expression level of SPP1 was significantly correlated with tumor grade. The expression level of SPP1 in the majority of tumor types were much higher than the corresponding normal tissues analyzed from databases. Besides, we also observed that high-expressed SPP1 was related to poor OS and DFS in LIHC, which supported the conclusion of meta-analysis. In addition, high-expressed SPP1 is related to 6 immune cells in TIME and DNA methylation regulatory genes. Ultimately, the results of Gene Set Enrichment Analysis (GSEA) suggested that tumor-related gene sets, such as hypoxia and lipid metabolism, were significantly enriched in high-expressed SPP1 group.Conclusions: SPP1 is high-expressed in various tumor tissues and correlated with poor prognosis. SPP1 might promote cancer invasion and metastasis by affecting tumor grade, TIME, DNA methylation, hypoxia, and lipid metabolism. SPP1 is expected to become a new clinical indicator for tumor detection and prognosis, and provide a new idea for tumor targeted therapy.


2020 ◽  
Author(s):  
Haoran Zheng ◽  
Ai-Min Jiang ◽  
Na Liu ◽  
Qian-Qian Ding ◽  
Fu-Mei Zhao ◽  
...  

Abstract Background: Several studies have investigated the relationship between secreted phosphoprotein 1 (SPP1) expression level and prognosis of various tumors, but the results are far from conclusive. Therefore, we performed the present meta-analysis to investigate the prognostic value of SPP1 in pan-cancer. Furthermore, a followed confirmation based on The Cancer Genome Atlas (TCGA) database was also performed to verify our results.Methods: We performed a systematic search from PubMed, Embase, Web of Science, and Cochrane Library databases and 19 articles, including 3403 patients and 9 types of tumors, were pooled in our meta-analysis. Overall survival (OS) and disease-free survival (DFS), which correlated with SPP1 expression, were considered as the primary outcome. Subgroup analyses, sensitivity analysis, and publication bias were used to investigate heterogeneity and reliability of the results. Furthermore, we also explored the relationship between SPP1 expression and clinical parameters of tumor patients. Finally, the results were verified with TCGA database and we further explored the relationship between SPP1 expression and tumor immuno-microenvironment (TIME), DNA methylation, and enriched gene pathway.Results: Our meta-analysis showed that high-expressed SPP1 was significantly related to poor OS and DFS in various cancers, especially in liver hepatocellular carcinoma (LIHC). Furthermore, we also identified that the high expression level of SPP1 was significantly correlated with tumor grade. The expression level of SPP1 in the majority of tumor types were much higher than the corresponding normal tissues analyzed from databases. Besides, we also observed that high-expressed SPP1 was related to poor OS and DFS in LIHC, which supported the conclusion of meta-analysis. In addition, high-expressed SPP1 is related to 6 immune cells in TIME and DNA methylation regulatory genes. Ultimately, the results of Gene Set Enrichment Analysis (GSEA) suggested that tumor-related gene sets, such as hypoxia and lipid metabolism, were significantly enriched in high-expressed SPP1 group.Conclusions: SPP1 is high-expressed in various tumor tissues and correlated with poor prognosis. SPP1 might promote cancer invasion and metastasis by affecting tumor grade, TIME, DNA methylation, hypoxia, and lipid metabolism. SPP1 is expected to become a new clinical indicator for tumor detection and prognosis, and provide a new idea for tumor targeted therapy.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4110
Author(s):  
Satoru Yonekura ◽  
Kosuke Ueda

Background: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. Methods: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE65904 and GSE19234). Results: The univariate and multivariate analyses showed that higher gene expression of EVI2B was significantly associated with longer prognoses. The EVI2B-high melanoma tissue had favorable histological parameters such as a brisk global distribution pattern and clustering structure of TILs (i.e., Banfield and Raftery index) with enriched CD8+ T cells over regulatory T cells and increased cytotoxicity scores. In addition, EVI2B expression positively correlated with IFN-γ signature genes (CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, and STAT1) and other various immunomodulatory genes. Conclusion: EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Feng-Juan Han ◽  
Jia Li ◽  
Ying Shen ◽  
Ying Guo ◽  
Yi-Chao Liu ◽  
...  

Abstract Objective Ovarian cancer (OC) has been regarded as the most malignant gynecological neoplasm and often confers grave outcomes owing to the frequent metastasis and high recurrence. A previous study has demonstrated that miR-1271-5p is implicated in OC progression, however, the possible mechanism of it remains unknown. The purpose of this investigation was to explore how miR-1271-5p regulates the progression of OC. Methods Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were employed to analyze the differentially expressed miRNAs or genes as well as their corresponding prognostic values. miR-1271-5p expression in OC cells was examined by qRT-PCR. Cell counting kit 8 (CCK-8), colony formation, and transwell tests were conducted to evaluate the proliferation, migration and invasion potentials. Bioinformatics prediction and luciferase activity analysis were utilized to predict and verify the target gene of miR-1271-5p. Western blot assay was carried out to measure protein expression. Results miR-1271-5p was significantly decreased in OC and its down-regulation was associated with the grave outcome of OC patients. Upregulation of miR-1271-5p inhibited cell viability, but miR-1271-5p knockdown promoted the proliferation of OC cells. TIAM1 was a direct target gene of miR-1271-5p and expressed in OC tissues at higher level. High expression of TIAM1 induced the poorer prognosis of patients with OC. Further functional analyses showed that the suppressive role of miR-1271-5p on OC cell malignant behaviors was overturned by the upregulation of TIAM1. The protein levels of Cyclin D1, HES1, NOTCH and NUMB were remarkably changed due to the abnormal expression of miR-1271-5p and TIAM1. Conclusion To sum up, miR-1271-5p inhibits proliferation, invasion and migration of OC cells by directly repressing TIAM1 to inactivate the Notch signaling pathway, which provides an alternative therapeutic candidate for the advancement of OC treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yixuan Li ◽  
Qian Cai ◽  
Ximing Shen ◽  
Xiaoting Chen ◽  
Zhong Guan

The immune checkpoint molecule, B7-H3, which belongs to the B7 family, has been shown to be overexpressed in various cancers. Its role in tumors is not well defined, and many studies suggest that it is associated with poor clinical outcomes. The effect of B7-H3 on laryngeal cancer has not been reported. This study investigated the expression of B7-H3 in laryngeal squamous cell carcinoma (LSCC), and its relationship with clinicopathological factors and prognosis of LSCC patients. The gene expression quantification data and clinical data of LSCC retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were analyzed to determine the diagnostic and prognostic roles of B7-H3. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed to determine the gene expression level of B7-H3 between LSCC tissues and paired normal adjacent tissues. In addition, TCGA RNA-seq data was analyzed to evaluate the expression level of B7 family genes. Next, the protein expression of B7-H3 and CD8 in LSCC was determined using immunohistochemistry and immunofluorescence. qRT-PCR results showed that the expression level of B7-H3 mRNA was significantly higher in LSCC tissues than in adjacent normal tissues. Similar results were obtained from the TCGA analysis. The expression of B7-H3 was significantly associated with T stage, lymph node metastasis, and pathological tumor node metastasis (TNM) stage, and it was also an independent factor influencing the overall survival time (OS) of patients with LSCC. In addition, B7-H3 was negatively correlated with CD8+T cells. These results show that B7-H3 is upregulated in LSCC. Therefore, B7-H3 may serve as a biomarker of poor prognosis and a promising therapeutic target in LSCC.


2021 ◽  
Author(s):  
Nuan Wang ◽  
Lijuan Yang ◽  
Da Yan ◽  
Xingfang Jia ◽  
Juanjuan Dai ◽  
...  

Abstract Background:Membrane-associated RING-CH 1 (MARCH1) is an E3 ubiquitin ligase that plays an important role in antigen presentation. The latest research found that MARCH1 can either promote or suppress cancer progression in ovarian, liver, and bladder cancers, but its function in gastric cancer has not been addressed. This study aimed to investigate the role of MARCH1 in gastric cancer.Methods:The Cancer Genome Atlas (TCGA) database was used to evaluate the expression level and biological function of MARCH1 in gastric cancer. We down-regulated and up-regulated the expression level of MARCH1 in gastric cancer cell line AGS by transfecting siRNAs and overexpression plasmids. Then we detected cell proliferation, migration, invasion and apoptosis using CCK-8 assay, transwell chamber assay and flow cytometry respectively. The relationship between MARCH1 and β-catenin was analyzed using western blotting assay. Results:The results showed that the expression of MARCH1 in gastric cancer was elevated and significantly related to clinical stage, tumor grade, and lymph node metastasis. It is worth noting that there was no significant correlation between the increase in MARCH1 expression level and overall survival. In addition, knocking down and upregulating the expression level of MARCH1 significantly affected the proliferation, migration, invasion, and apoptosis of gastric cancer cells. Furthermore, the study found that MARCH1 and β-catenin positively regulated each other, suggesting that MARCH1 may participate in the malignant biological behavior of tumors through the Wnt/β-catenin pathway.Conclusions:In summary, this study shows the function of MARCH1 in the progression of gastric cancer and provides unique insights into the regulatory mechanism of MARCH1 and β-catenin, which indicates that MARCH1 may be a new target molecule for gastric cancer.


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