scholarly journals Identification of hub genes associated with prognosis, diagnosis, immune infiltration and therapeutic drug in liver cancer by integrated analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Xinyi Lei ◽  
Miao Zhang ◽  
Bingsheng Guan ◽  
Qiang Chen ◽  
Zhiyong Dong ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Liver Cancer ◽  
The Cancer Genome Atlas ◽  
Integrated Analysis ◽  
Therapeutic Drug ◽  
Mrna Levels ◽  
Hub Genes ◽  
Protein Levels ◽  
Tumor Infiltrate ◽  
The Relationship

Abstract Background Liver cancer is one of the most common cancers and causes of cancer death worldwide. The objective was to elucidate novel hub genes which were benefit for diagnosis, prognosis, and targeted therapy in liver cancer via integrated analysis. Methods GSE84402, GSE101685, and GSE112791 were filtered from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified by using the GEO2R. The GO and KEGG pathway of DEGs were analyzed in the DAVID. PPI and TF network of the DEGs were constructed by using the STRING, TRANSFAC, and Harmonizome. The relationship between hub genes and prognoses in liver cancer was analyzed in UALCAN based on The Cancer Genome Atlas (TCGA). The diagnostic value of hub genes was evaluated by ROC. The relationship between hub genes and tumor-infiltrate lymphocytes was analyzed in TIMER. The protein levels of hub genes were verified in HPA. The interaction between the hub genes and the drug were identified in DGIdb. Results In total, 108 upregulated and 60 downregulated DEGs were enriched in 148 GO terms and 20 KEGG pathways. The mRNA levels and protein levels of CDK1, HMMR, PTTG1, and TTK were higher in liver cancer tissues compared to normal tissues, which showed excellent diagnostic and prognostic value. CDK1, HMMR, PTTG1, and TTK were positively correlated with tumor-infiltrate lymphocytes, which might involve tumor immune response. The CDK1, HMMR, and TTK had close interaction with anticancer agents. Conclusions The CDK1, HMMR, PTTG1, and TTK were hub genes in liver cancer; hence, they might be potential biomarkers for diagnosis, prognosis, and targeted therapy of liver cancer.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

Screening of cervical cancer-related hub genes based on comprehensive bioinformatics analysis

2021 ◽  
pp. 1-13
Author(s):  
Simei Tu ◽  
Hao Zhang ◽  
Xiaocheng Yang ◽  
Wen Wen ◽  
Kangjing Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Hub Genes ◽  
Normal Tissues ◽  
Significant Difference ◽  
Core Genes

BACKGROUND: Since the molecular mechanisms of cervical cancer (CC) have not been completely discovered, it is of great significance to identify the hub genes and pathways of this disease to reveal the molecular mechanisms of cervical cancer. OBJECTIVE: The study aimed to identify the biological functions and prognostic value of hub genes in cervical cancer. METHODS: The gene expression data of CC patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The core genes were screened out by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). R software, the STRING online tool and Cytoscape software were used to screen out the hub genes. The GEPIA public database was used to further verify the expression levels of the hub genes in normal tissues and tumour tissues and determine the disease-free survival (DFS) rates of the hub genes. The protein expression of the survival-related hub genes was identified with the Human Protein Atlas (HPA) database. RESULTS: A total of 64 core genes were screened, and 10 genes, including RFC5, POLE3, RAD51, RMI1, PALB2, HDAC1, MCM4, ESR1, FOS and E2F1, were identified as hub genes. Compared with that in normal tissues, RFC5, POLE3, RAD51,RMI1, PALB2, MCM4 and E2F1 were all significantly upregulated in cervical cancer, ESR1 was significantly downregulated in cervical cancer, and high RFC5 expression in CC patients was significantly related to OS. In the DFS analysis, no significant difference was observed in the expression level of RFC5 in cervical cancer patients. Finally, RFC5 protein levels verified by the HPA database were consistently upregulated with mRNA levels in CC samples. CONCLUSIONS: RFC5 may play important roles in the occurrence and prognosis of CC. It could be further explored and validated as a potential predictor and therapeutic target for CC.

scholarly journals Identification of FOS as a Candidate Risk Gene for Liver Cancer by Integrated Bioinformatic Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jin-Wu Hu ◽  
Guang-Yu Ding ◽  
Pei-Yao Fu ◽  
Wei-Guo Tang ◽  
Qi-Man Sun ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Liver Tumors ◽  
Prognostic Significance ◽  
Bioinformatic Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Time To Recurrence ◽  
Mitogen Activated Protein ◽  
Novel Therapeutic

Liver cancer is a lethal disease that is associated with poor prognosis. In order to identify the functionally important genes associated with liver cancer that may reveal novel therapeutic avenues, we performed integrated analysis to profile miRNA and mRNA expression levels for liver tumors compared to normal samples in The Cancer Genome Atlas (TCGA) database. We identified 405 differentially expressed genes and 233 differentially expressed miRNAs in tumor samples compared with controls. In addition, we also performed the pathway analysis and found that mitogen-activated protein kinases (MAPKs) and G-protein coupled receptor (GPCR) pathway were two of the top significant pathway nodes dysregulated in liver cancer. Furthermore, by examining these signaling networks, we discovered that FOS (Fos proto-oncogene, AP-1 transcription factor subunit), LAMC2 (laminin subunit gamma 2), and CALML3 (calmodulin like 3) were the most significant gene nodes with high degrees involved in liver cancer. The expression and disease prediction accuracy of FOS, LAMC2, CALML3, and their interacting miRNAs were further performed using a HCC cohort. Finally, we investigated the prognostic significance of FOS in another HCC cohort. Patients with higher FOS expression displayed significantly shorter time to recurrence (TTR) and overall survival (OS) compared with patients with lower expression. Collectively, our study demonstrates that FOS is a potential prognostic marker for liver cancer that may reveal a novel therapeutic avenue in this lethal disease.

scholarly journals The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ruobing Wang ◽  
Yan Jiao ◽  
Yanqing Li ◽  
Siyang Ye ◽  
Guoqiang Pan ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Mrna Expression ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Inositol Polyphosphate ◽  
Chi Square ◽  
Cancer Genome Atlas ◽  
Poor Outcomes ◽  
The Relationship

Liver cancer is a devastating disease for humans with poor prognosis. Although the survival rate of patients with liver cancer has improved in the past decades, the recurrence and metastasis of liver cancer are still obstacles for us. Inositol polyphosphate-5-phosphatase K (INPP5K) belongs to the family of phosphoinositide 5-phosphatases (PI 5-phosphatases), which have been reported to be associated with cell migration, polarity, adhesion, and cell invasion, especially in cancers. However, there have been few studies on the correlation of INPP5K and liver cancer. In this study, we explored the prognostic significance of INPP5K in liver cancer through bioinformatics analysis of data collected from The Cancer Genome Atlas (TCGA) database. Chi-square and Fisher exact tests were used to evaluate the relationship between INPP5K expression and clinical characteristics. Our results showed that low INPP5K expression was correlated with poor outcomes in liver cancer patients. Univariate and multivariate Cox analyses demonstrated that low INPP5K mRNA expression played a significant role in shortening overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for liver cancer. In conclusion, low INPP5K mRNA expression is an independent risk factor for poor prognosis in liver cancer.

scholarly journals IL-33/ST2 axis promotes the inflammatory response of nasal mucosal epithelial cells through inducing the ERK1/2 pathway

2020 ◽  
Vol 26 (6) ◽  
pp. 505-513
Author(s):  
Yun-Qiu Li ◽  
Yu Zhong ◽  
Xu-Ping Xiao ◽  
Dan-Dan Li ◽  
Zheng Zhou ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ar Model ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
Model Group ◽  
Protein Levels ◽  
Tnf Α ◽  
Der P1 ◽  
The Relationship

Allergic rhinitis (AR) is a nasal mucosal inflammatory disease mediated by environmental allergens. At present, the relationship between the IL-33/ST2 axis, ERK1/2 pathway and AR progression needs further exploration. In our study, an AR model was constructed in vitro by treating HNEpC cells with Der p1. qRT-PCR was applied to assess the mRNA levels of IL-33, ST2, TNF-α, IL-6, and IL-8. Western blotting was used to measure the protein levels of IL-33, ST2, and the downstream proteins p-ERK1/2, ERK1/2, p-RSK, and RSK. IL-6, IL-8, IL-33, and TNF-α protein levels in cell supernatants were evaluated by ELISA. Flow cytometry was performed to check cell apoptosis of HNEpC in the presence or absence of Der p1. Our results indicate that the relative levels of IL-33, ST2, TNF-α, IL-6, and IL-8 were increased significantly in the AR model group. The above effects were notably reversed after transfection with shIL-33 or shST2. IL-33 stimulation further resulted in the increase in both ST2 and inflammation-associated cytokines, and these effects were restored after shST2 treatment. Also, the levels of inflammatory factors induced by IL-33 stimulation or ST2 overexpression were reversed after applying an ERK1/2 pathway blocker. In conclusion, IL-33/ST2 mediated inflammation of nasal mucosal epithelial cells by inducing the ERK1/2 pathway.

Relationship of ERCC1 genotype variant with mRNA expression and ERCC1 protein levels in advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 260-260
Author(s):  
Elizabeth A. Guancial ◽  
Lillian Werner ◽  
Joaquim Bellmunt ◽  
Nikitas Nikitas ◽  
Edward C. Stack ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Excision Repair ◽  
Predictive Biomarker ◽  
Mrna Levels ◽  
Nuclear Staining ◽  
Protein Levels ◽  
Tissue Arrays ◽  
Platinum Based Chemotherapy ◽  
The Relationship

260 Background: DNA repair factors may be predictive for response to chemotherapies that produce DNA damage. While low ERCC1 protein and mRNA levels have been reported as associated with improved outcomes in metastatic UC patients treated with platinum-based chemotherapy, the relationship between genotype, mRNA expression, and protein level is unknown. The ERCC1 germline 19007C>T single-nucleotide polymorphism (SNP) is functionally associated with reduced translation of ERCC1 mRNA. We investigated the relationship between ERCC1 germline SNP, ERCC1 tumor mRNA and protein expression, in a cohort of patients with advanced UC who received first-line, platinum-based chemotherapy. Methods: A cohort of clinically annotated, uniformly-treated advanced UC patients with FFPE primary tumor tissue available was identified through the Hellenic cooperative Oncology Group (HECOG) (N=93). Genomic DNA extraction, nested PCR, and restriction fragment length polymorphism techniques for the 19007C>T SNP were performed to identify C/C, C/T and T/T genotypes. ERCC1 mRNA expression was interrogated using Nanostring nCounter profiling. IHC analysis was performed on tissue arrays using an ERCC1 antibody. Percent of positive nuclear staining was categorized as quartiles using previously identified cut-points. Results: ERCC1 C/T genotype was identified in 30/61 samples (49%) and T/T in 14/61 samples (23%). In 54 patients with both SNP and mRNA data available, T/T genotype was associated with the highest level of mRNA expression, followed by the C/T genotype (p=0.04). Neither ERCC1 genotype (N=44) nor ERCC1 mRNA expression (N=54) was associated with ERCC1 protein expression as measured by IHC (p=0.52 and p=0.13, respectively). Conclusions: ERCC1 19007C>T is associated with increased ERCC1 mRNA expression. However, neither genotype nor mRNA are surrogates for ERCC1 protein detected by IHC in advanced UC tumors. This suggests that while genotype influences mRNA expression of ERCC1, the use of the nucleotide excision repair pathway as a predictive biomarker of platinum-sensitivity may be more complex than previously appreciated and require the integrative use of proteomics, genomics and epigenomics.

scholarly journals ATG101 as a Novel Prognostic Biomarker Related to Immunotherapy in Pan-cancer

2021 ◽  
Author(s):  
Zijian Zhang ◽  
Jinggang Mo ◽  
Chong Jin ◽  
Hao Jiang ◽  
Zhongtao Liu ◽  
...  
Keyword(s):  
Critical Role ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Integrated Analysis ◽  
Tumour Immunity ◽  
Kaplan Meier ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Pan Cancer

Abstract Background: ATG101 plays a significant role in the occurrence and development of tumours by regulating autophagy. Our study aimed to research the correlation between the expression of ATG101 and tumour prognosis and its role in tumour immunity. Methods: First, integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals were used to analyse the expression of ATG101. Then, we used Kaplan–Meier curves for survival analysis. Next, we analysed the relationship between ATG101 expression and six immune cells, the immune microenvironment and immune checkpoints. Besides, we analysed the relationship between the expression of ATG101 and methyltransferase. Finally, we used GSEA to study the function of ATG101 in COAD and LIHC. Results: Integrated analysis showed that ATG101 was overexpressed in different tumours. Kaplan–Meier curves found that ATG101 was associated with poor prognosis in most tumours. We found that that ATG101 can be used as a target and prognostic marker of tumour immunotherapy for different tumours. We also found that ATG101 regulates DNA methylation. GSEA analysis showed that ATG101 may play a critical role in COAD and LIHC.Conclusions: Our study highlights the significance of ATG101 in the study of tumour immunity from a pan-cancer perspective.

scholarly journals Identification of Key Prognostic Biomarker and Its Correlation with Immune Infiltrates in Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Hong Luan ◽  
Chuang Zhang ◽  
Tuo Zhang ◽  
Ye He ◽  
Yanna Su ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Immune Therapy ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Hub Genes ◽  
Immune Infiltration ◽  
The Relationship

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor. The immune profile of PDAC and the immunologic milieu of its tumor microenvironment (TME) are unique; however, the mechanism of how the TME engineers the carcinogenesis of PDAC is not fully understood. This study is aimed at better understanding the relationship between the immune infiltration of the TME and gene expression and identifying potential prognostic and immunotherapeutic biomarkers for PDAC. Analysis of data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases identified differentially expressed genes (DEGs), including 159 upregulated and 53 downregulated genes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment were performed and showed that the DEGs were mainly enriched for the PI3K-Akt signaling pathway and extracellular matrix organization. We used the cytoHubba plugin of Cytoscape to screen out the most significant ten hub genes by four different models (Degree, MCC, DMNC, and MNC). The expression and clinical relevance of these ten hub genes were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. High expression of nine of the hub genes was positively correlated with poor prognosis. Finally, the relationship between these hub genes and tumor immunity was analyzed using the Tumor Immune Estimation Resource. We found that the expression of SPARC, COL6A3, and FBN1 correlated positively with infiltration levels of six immune cells in the tumors. In addition, these three genes had a strong coexpression relationship with the immune checkpoints. In conclusion, our results suggest that nine upregulated biomarkers are related to poor prognosis in PDAC and may serve as potential prognostic biomarkers for PDAC therapy. Furthermore, SPARC, COL6A3, and FBN1 play an important role in tumor-related immune infiltration and may be ideal targets for immune therapy against PDAC.

Bioinformatics Combined with Quantitative Proteomics Analyses and Identification of Potential Biomarkers in Cholangiocarcinoma

2020 ◽  
Author(s):  
Zijian Da ◽  
Long Gao ◽  
Gang Su ◽  
Jia Yao ◽  
Wenkang Fu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Poor Prognosis ◽  
Independent Risk Factor ◽  
Primary Tumour ◽  
Absolute Quantification ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Protein Levels

Abstract Background Cholangiocarcinoma(CCA)is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis. Methods The GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed. Results Through bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients. Conclusions CASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.

scholarly journals Identification of potential biomarkers and candidate small molecule drugs in glioblastoma

2020 ◽  
Author(s):  
Wei-cheng Lu ◽  
Hui Xie ◽  
Ce Yuan ◽  
Jin-jiang Li ◽  
Zhao-yang Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Hub Genes ◽  
Expression Levels ◽  
Small Molecule Drugs ◽  
Key Genes

Abstract Background and aims:Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM. Methods:Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein-protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database. Results:A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM. Conclusions:Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.

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