scholarly journals The nine ADAMs family members serve as potential biomarkers for immune infiltration in pancreatic adenocarcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9736
Author(s):  
Bing Qi ◽  
Han Liu ◽  
Ying Dong ◽  
Xueying Shi ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Family Members ◽  
Tumor Grade ◽  
Immune Checkpoint Blockade ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Number Variation ◽  
Adams Family ◽  
Significant Expression

Background The functional significance of ADAMs family members in the immune infiltration of pancreatic adenocarcinoma (PAAD) awaits elucidation. Methods ADAMs family members with significant expression were identified among differentially expressed genes of PAAD based on The Cancer Genome Atlas (TCGA) database followed by a verification based on the Oncomine database. The correlation of ADAMs in PAAD was estimated with the Spearman’s rho value. The pathway enrichment of ADAMs was performed by STRING and GSEALite, respectively. The protein–protein interaction and Gene Ontology analyses of ADAMs and their similar genes were exanimated in STRING and visualized by Cytoscape. Subsequently, the Box-Whisker plot was used to show a correlation between ADAMs and different tumor grade 1/2/3/4 with Student’s t-test. TIMER was applied to estimate a correlation of ADAMs expressions with immune infiltrates and immune checkpoint blockade (ICB) immunotherapy-related molecules. Furthermore, the effect of copy number variation (CNV) of ADAMs genes was assessed on the immune infiltration levels. Result ADAM8/9/10/12/15/19/28/TS2/TS12 were over-expressed in PAAD. Most of the nine ADAMs had a significant correlation. ADAM8/12/15/19 expression was remarkably increased in the comparison between grade 1 and grade 2/3 of PAAD. ADAM8/9/10/12/19/28/TS2/TS12 had a positive correlation with almost five immune infiltrates. ADAM12/19/TS2/TS12 dramatically related with ICB immunotherapy-related molecules. CNV of ADAMs genes potentially influenced the immune infiltration levels. Conclusion Knowledge of the expression level of the ADAMs family could provide a reasonable strategy for improved immunotherapies to PAAD.

scholarly journals CXCL10 is a Tumor Microenvironment and Immune Infiltration Related Prognostic Biomarker in Pancreatic Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Huimin Huang ◽  
Wangxiao Zhou ◽  
Renpin Chen ◽  
Bingfeng Xiang ◽  
Shipeng Zhou ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Pancreatic Adenocarcinoma ◽  
Cox Regression ◽  
Predictive Biomarker ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
Protein Protein Interaction ◽  
Novel Biomarkers

Pancreatic adenocarcinoma (PAAD) is the 10th most common cancer worldwide and the outcomes for patients with the disease remain extremely poor. Precision biomarkers are urgently needed to increase the efficiency of early diagnosis and to improve the prognosis of patients. The tumor microenvironment (TME) and tumor immune infiltration are thought to impact the occurrence, progression, and prognosis of PAAD. Novel biomarkers excavated originating from the TME and immune infiltration may be effective in predicting the prognosis of PAAD patients. In the current study, the ESTIMATE and CIBERSORT algorithms were applied to estimate the division of immune and stromal components and the proportion of tumor-infiltrating immune cells in 182 PAAD cases downloaded from The Cancer Genome Atlas database. Intersection analyses of the Protein-Protein Interaction networks and Cox regression analysis identified the chemokine (CXC-motif) ligand 10 (CXCL10) as a predictive biomarker. We verified that CXCL10 in the TME negatively correlates with prognosis in PAAD and positively correlates with tumor cell differentiation. GSE62452 from the GEO database and cumulative survival analysis were performed to validate CXCL10 expression as an independent prognostic indicator. We also found that memory B cells, regulatory T cells, and macrophages M0 and M1 were correlated with the expression of CXCL10 indicating that expression of CXCL10 influenced the immune activity of the TME. Our data suggest that CXCL10 is beneficial as a prognostic indicator in PAAD patients and highlights the potential for immune targeted therapy in the treatment of PAAD.

Prognostic Value and Immune Infiltration of ARMC10 in Pancreatic Adenocarcinoma Via Integrated Bioinformatics Analyses

2021 ◽  
Author(s):  
Tianhao Li ◽  
Xiaohan Qin ◽  
Cheng Qin ◽  
Bangbo Zhao ◽  
Hongtao Cao ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Formation Rate ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Primary Therapy ◽  
Migration Ability ◽  
Bioinformatics Analyses ◽  
Immune Infiltration

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.

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 Interferon regulatory factor family influences tumor immunity and prognosis of patients with colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan-Jie Chen ◽  
Shu-Neng Luo ◽  
Ling Dong ◽  
Tao-Tao Liu ◽  
Xi-Zhong Shen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Noncoding Rna ◽  
Immune Cell ◽  
Family Members ◽  
Interferon Regulatory Factor ◽  
The Cancer Genome Atlas ◽  
Regulatory Factor ◽  
Clinical Prognosis ◽  
Immune Infiltration

Abstract Background Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC. Methods Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein–protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples. Results Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages. Conclusions On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.

scholarly journals GNG7 and ADCY1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma through bioinformatic-based analyses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youfu Zhang ◽  
Jinran Yang ◽  
Xuyang Wang ◽  
Xinchang Li
Keyword(s):  
Survival Analysis ◽  
Pancreatic Adenocarcinoma ◽  
Cox Regression ◽  
Malignant Tumors ◽  
The Cancer Genome Atlas ◽  
Prognostic Biomarkers ◽  
Cox Regression Analysis ◽  
Protein Protein Interaction ◽  
Kegg Analysis ◽  
Upregulated Genes

AbstractPancreatic adenocarcinoma (PAAD) is one of the most lethal malignant tumors in the world. The GSE55643 and GSE15471 microarray datasets were downloaded to screen the diagnostic and prognostic biomarkers for PAAD. 143 downregulated genes and 118 upregulated genes were obtained. Next, we performed gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on these genes and constructed a protein–protein interaction (PPI) network. We screened out two important clusters of genes, including 13 upregulated and 5 downregulated genes. After the survival analysis, 3 downregulated genes and 10 upregulated genes were identified as the selected key genes. The KEGG analysis on 13 selected genes showed that GNG7 and ADCY1 enriched in the Pathway in Cancer. Next, the diagnostic and prognostic value of GNG7 and ADCY1 was investigated using independent cohort of the Cancer Genome Atlas (TCGA), GSE84129 and GSE62452. We observed that the expression of the GNG7 and ADCY1 was decreased in PAAD. The diagnostic receiver operating characteristic (ROC) analysis indicated that the GNG7 and ADCY1 could serve as sensitive diagnostic markers in PAAD. Survival analysis suggested that expression of GNG7, ADCY1 were significantly associated with PAAD overall survival (OS). The multivariate cox regression analysis showed that the expression of GNG7, ADCY1 were independent risk factors for PAAD OS. Our study indicated GNG7 and ADCY1 may be potential diagnostic and prognostic biomarkers in patients with PAAD.

scholarly journals Identification of Potential Driver Genes Based on Multi-Genomic Data in Cervical Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuexun Xu ◽  
Hui Luo ◽  
Qunchao Hu ◽  
Haiyan Zhu
Keyword(s):  
Cervical Cancer ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Driver Genes ◽  
Molecular Alterations ◽  
Wide Range ◽  
Number Variation ◽  
Cancer Genome Atlas ◽  
Significant Expression

Background: Cervical cancer became the third most common cancer among women, and genome characterization of cervical cancer patients has revealed the extensive complexity of molecular alterations. However, identifying driver mutation and depicting molecular classification in cervical cancer remain a challenge.Methods: We performed an integrative multi-platform analysis of a cervical cancer cohort from The Cancer Genome Atlas (TCGA) based on 284 clinical cases and identified the driver genes and possible molecular classification of cervical cancer.Results: Multi-platform integration showed that cervical cancer exhibited a wide range of mutation. The top 10 mutated genes were TTN, PIK3CA, MUC4, KMT2C, MUC16, KMT2D, SYNE1, FLG, DST, and EP300, with a mutation rate from 12 to 33%. Applying GISTIC to detect copy number variation (CNV), the most frequent chromosome arm-level CNVs included losses in 4p, 11p, and 11q and gains in 20q, 3q, and 1q. Then, we performed unsupervised consensus clustering of tumor CNV profiles and methylation profiles and detected four statistically significant expression subtypes. Finally, by combining the multidimensional datasets, we identified 10 potential driver genes, including GPR107, CHRNA5, ZBTB20, Rb1, NCAPH2, SCA1, SLC25A5, RBPMS, DDX3X, and H2BFM.Conclusions: This comprehensive analysis described the genetic characteristic of cervical cancer and identified novel driver genes in cervical cancer. These results provide insight into developing precision treatment in cervical cancer.

scholarly journals Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Chongli Zhang ◽  
Yong Cui ◽  
Guannan Wang ◽  
Wugan Zhao ◽  
Haiyu Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Family Members ◽  
Tumor Grade ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Immune Infiltration ◽  
E2f Transcription Factors ◽  
Mrna Expression Levels

Background. E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Methods. We used online databases, such as ONCOMINE, UALCAN, Kaplan–Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results. Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients ( P  = 3.9E – 06), while high mRNA expression of E2F6 is not related to OS ( P  = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients ( P  = 7.094E – 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions. These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.

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

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.

scholarly journals Identification of glycolysis related pathways in pancreatic adenocarcinoma and liver hepatocellular carcinoma based on TCGA and GEO datasets

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ji Li ◽  
Chen Zhu ◽  
Peipei Yue ◽  
Tianyu Zheng ◽  
Yan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Energy Metabolism ◽  
Pancreatic Adenocarcinoma ◽  
Digestive System ◽  
Prognostic Significance ◽  
R Package ◽  
The Cancer Genome Atlas ◽  
System Structure ◽  
Liver Hepatocellular Carcinoma

Abstract Background Abnormal energy metabolism is one of the characteristics of tumor cells, and it is also a research hotspot in recent years. Due to the complexity of digestive system structure, the frequency of tumor is relatively high. We aim to clarify the prognostic significance of energy metabolism in digestive system tumors and the underlying mechanisms. Methods Gene set variance analysis (GSVA) R package was used to establish the metabolic score, and the score was used to represent the metabolic level. The relationship between the metabolism and prognosis of digestive system tumors was explored using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Volcano plots and gene ontology (GO) analyze were used to show different genes and different functions enriched between different glycolysis levels, and GSEA was used to analyze the pathway enrichment. Nomogram was constructed by R package based on gene characteristics and clinical parameters. qPCR and Western Blot were applied to analyze gene expression. All statistical analyses were conducted using SPSS, GraphPad Prism 7, and R software. All validated experiments were performed three times independently. Results High glycolysis metabolism score was significantly associated with poor prognosis in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). The STAT3 (signal transducer and activator of transcription 3) and YAP1 (Yes1-associated transcriptional regulator) pathways were the most critical signaling pathways in glycolysis modulation in PAAD and LIHC, respectively. Interestingly, elevated glycolysis levels could also enhance STAT3 and YAP1 activity in PAAD and LIHC cells, respectively, forming a positive feedback loop. Conclusions Our results may provide new insights into the indispensable role of glycolysis metabolism in digestive system tumors and guide the direction of future metabolism–signaling target combined therapy.

scholarly journals RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Transcription Factor ◽  
Low Frequency ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Wild Type ◽  
Lower Grade Glioma ◽  
Cancer Genome Atlas ◽  
Worse Prognosis ◽  
Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

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