scholarly journals Comprehensive analysis of tumour mutational burden and its clinical significance in prostate cancer

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lijuan Wang ◽  
Shucheng Pan ◽  
Binbin Zhu ◽  
Zhenliang Yu ◽  
Wei Wang
Keyword(s):  
Prostate Cancer ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Comprehensive Analysis ◽  
Functional Enrichment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dna Mutation ◽  
Mutational Burden

Abstract Background The tumorigenesis of prostate cancer involves genetic mutations. Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immunotherapy. Results Single-nucleotide polymorphisms were the most common variant type, and C>T transversion was the most commonly presented type of single-nucleotide variant. The high-TMB group had lower overall survival (OS) than the low-TMB group. TMB was associated with age, T stage and N stage. Functional enrichment analysis of differentially expressed genes (DEGs) showed that they are involved in pathways related to the terms spindle, chromosomal region, nuclear division, chromosome segregation, cell cycle, oocyte meiosis and other terms associated with DNA mutation and cell proliferation. Six hub genes, PLK1, KIF2C, MELK, EXO1, CEP55 and CDK1, were identified. All the genes were associated with disease-free survival, and CEP55 and CDK1 were associated with OS. Conclusions The present study provides a comprehensive analysis of the significance of TMB and DEGs and infiltrating immune cells related to TMB, which provides helpful information for exploring the significance of TMB in prostate cancer.

scholarly journals miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets

2020 ◽  
Vol 49 (D1) ◽  
pp. D1276-D1281
Author(s):  
Chun-Jie Liu ◽  
Xin Fu ◽  
Mengxuan Xia ◽  
Qiong Zhang ◽  
Zhifeng Gu ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Mirna Target ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Nucleotide Polymorphisms ◽  
Functional Variation ◽  
Single Nucleotide ◽  
Target Binding

Abstract MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3′UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.

scholarly journals Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yu Sun ◽  
Sheng-Hua Li ◽  
Ji-Wen Cheng ◽  
Gang Chen ◽  
Zhi-Guang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Protein Level ◽  
Target Genes ◽  
Mrna Level ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Forest Plot ◽  
Biological Mechanism

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

Integrative Analysis of four miRNA prognostic signatures of prostate cancer

2020 ◽  
Author(s):  
Chen Chi ◽  
Xianwu Chen ◽  
Liping Yao ◽  
Min Li ◽  
Lanting Xiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Relationship Of

Abstract Background Prostate cancer (PCa) is the most common urological cancer among men, having a poor prognosis, which is hard to accurately evaluate based on the present methods. MicroRNAs (miRNAs), a class of internal non-coding small RNA, can involve in the regulation of tumor biological function. So far, many researchers have tried to explore the relationship of malignant progress of PCa with miRNA, while there are just limited studies conducting the comprehensive analysis of miRNA in PCa clinical significance. Methods The data of miRNA and mRNA expressions in PCa were downloaded from TCGA database, and were performed the overall survival (OS) analysis using Survival package of R software to harvest the differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs). The bioinformatics tools such as TargetScan, miRDB, and miRanda were also conducted to forecast the desired target genes related with prognostic DEMs. In addition, both GO and KEGG analyses were used to uncover the fundamental signaling pathways and cellular processes in PCa as well as the protein-protein interaction (PPI) network was constructed through STRING and Cytoscape software. Results Firstly, 4 DEMs (miR-19a-3p, miR-144-3p, miR-223-5p, and miR-483-3p) were found having significantly associated with overall survival in PCa. Based on the criteria with FDR < 0.05 and |log2FC| > 1, 33 genes were screened out as DEGs. Besides, the functional enrichment analysis revealed that these DEGs of 4 miRNAs may participate in cancer-related pathways like FoxO and PI3K-Akt signaling pathway. Lastly, the low expression of CD177 may be potentially associated with poor survival of patients in PCa. Conclusion This study systematically analyzed multiple PCa prognostic DEMs (miR-19a-3p, miR-144-3p, miR-223-5p, and miR-483-3p), and verified a novel DEG signature (CD177) that can be used to effectively assess the prognosis of PCa patients.

scholarly journals Identification of Key MicroRNAs and Mechanisms in Prostate Cancer Evolution Based on Biomarker Prioritization Model and Carcinogenic Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuxin Lin ◽  
Zhijun Miao ◽  
Xuefeng Zhang ◽  
Xuedong Wei ◽  
Jianquan Hou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cancer Evolution ◽  
Network Systems ◽  
Holistic Management ◽  
Study Gene Expression ◽  
Association Data ◽  
Translational Informatics

Background: Prostate cancer (PCa) is occurred with increasing incidence and heterogeneous pathogenesis. Although clinical strategies are accumulated for PCa prevention, there is still a lack of sensitive biomarkers for the holistic management in PCa occurrence and progression. Based on systems biology and artificial intelligence, translational informatics provides new perspectives for PCa biomarker prioritization and carcinogenic survey.Methods: In this study, gene expression and miRNA-mRNA association data were integrated to construct conditional networks specific to PCa occurrence and progression, respectively. Based on network modeling, hub miRNAs with significantly strong single-line regulatory power were topologically identified and those shared by the condition-specific network systems were chosen as candidate biomarkers for computational validation and functional enrichment analysis.Results: Nine miRNAs, i.e., hsa-miR-1-3p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-182-5p, hsa-miR-198, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-34a-5p, and hsa-miR-499a-5p, were prioritized as key players for PCa management. Most of these miRNAs achieved high AUC values (AUC &gt; 0.70) in differentiating different prostate samples. Among them, seven of the miRNAs have been previously reported as PCa biomarkers, which indicated the performance of the proposed model. The remaining hsa-miR-22-3p and hsa-miR-499a-5p could serve as novel candidates for PCa predicting and monitoring. In particular, key miRNA-mRNA regulations were extracted for pathogenetic understanding. Here hsa-miR-145-5p was selected as the case and hsa-miR-145-5p/NDRG2/AR and hsa-miR-145-5p/KLF5/AR axis were found to be putative mechanisms during PCa evolution. In addition, Wnt signaling, prostate cancer, microRNAs in cancer etc. were significantly enriched by the identified miRNAs-mRNAs, demonstrating the functional role of the identified miRNAs in PCa genesis.Conclusion: Biomarker miRNAs together with the associated miRNA-mRNA relations were computationally identified and analyzed for PCa management and carcinogenic deciphering. Further experimental and clinical validations using low-throughput techniques and human samples are expected for future translational studies.

scholarly journals Whole-genome sequencing of a Brazilian naturalized horse breed resistant to arid climate for identifying single nucleotide variants and insertions/deletions

2020 ◽  
Author(s):  
Danielle Cunha Cardoso ◽  
Eduardo Geraldo Alves Coelho ◽  
Brenda Neves Porto ◽  
glacy silva ◽  
Denea de Araújo Fernandes Pires ◽  
...  
Keyword(s):  
Variant Calling ◽  
Olfactory Receptors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Single Nucleotide Variants ◽  
Horse Breed ◽  
Single Nucleotide ◽  
Arid Conditions ◽  
Single Nucleotide Variations

Abstract Background: In this study, we perform a search for variants (SNVs and InDels) in the genome of a Brazilian Naturalized horse breed, using FreeBayes and GATK variant calling tools. This breed presents exclusive adaptive traits of extreme importance to semi-arid conditions, such as those that allow survival under excessive sunlight, rainfall, low forage availability and stony ground. Moreover, these traits are expressed without any detriment to the performance and perpetuation of the breed. Results: A total of 305,588,364 reads were mapped in the horse reference genome, 1,598,210 single nucleotide variations and 138,139 insertions/deletions were detected by FreeBayes, 88,838 (SNVs) and 25,232 (InDels) by GATK. Both have been used in order to increase the safety of variant calls, identify in which regions of the genome they are present and check for variants in genes possibly associated with the peculiar traits exhibited by the breed. Conclusions: The variants annotation identified numerous non-synonymous SNVs and frameshift InDels, which could affect phenotypic variation. We found 28 and 392 Emsembl gene IDs containing high and moderate impact SNVs, including GTPase family members, olfactory receptors, mitochondrial complex and defense genes. Functional enrichment analysis was performed and revealed that variants in the olfactory transduction pathway were overrepresented.

scholarly journals Predictive Value of CCNB1, BUB1B and TTK in the Progression and Prognosis of Lung Adenocarcinoma

2020 ◽  
Author(s):  
Lecai Xiong ◽  
Yuquan Bai ◽  
Minglin Zhu ◽  
Zetian Yang ◽  
Jinping Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Lung Cancer Patients

Lung cancer predominates in cancer-related deaths worldwide, with lung adenocarcinoma (LUAD) being a common histological subtype of lung cancer. The aim at this study was to search for biomarkers associated with the progression and prognosis of LUAD. We have integrated the expression profiles of 1174 lung cancer patients from five GEO datasets (GSE18842, GSE19804, GSE30219, GSE40791 and GSE68465) and identified a set of differentially expressed genes. Functional enrichment analysis showed that these genes are closely related to the progression of LUAD, such as cell cycle, mitosis and adhesion. Cytoscape software was used to establish a protein-protein interaction (PPI) network to analyze important modules using Molecular Complex Detection (MCODE), and finally CCNB1, BUB1B and TTK were selected for further study. The study found that compared with non-tumor lung tissue, CCNB1, BUB1B and TTK are highly expressed in LUAD. Kaplan-Meier analysis showed that CCNB1, BUB1B and TTK were negatively correlated with the overall survival and disease-free survival of patients. Gene set enrichment analysis (GSEA) demonstrated that for the samples of any hub gene highly expressed, most of the functional gene sets enriched in cell cycle. In summary, CCNB1, BUB1B and TTK can be used as biomarkers of poor prognosis of LUAD. The high expression of CCNB1, BUB1B and TTK can accelerate the progression of LUAD and lead to shorter survival, suggesting that they may be potential targets for treatment in LUAD.

Investigation of Key Genes associated with Prostate Cancer using RNA-Seq Data

2014 ◽  
Vol 29 (1) ◽  
pp. e86-e92 ◽  
Author(s):  
Jitao Wu ◽  
Fan Feng ◽  
Diandong Yang ◽  
Shengqiang Yu ◽  
Jianqiu Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Normal Sample ◽  
Pathway Enrichment Analysis ◽  
Rna Seq ◽  
Cancer Sample ◽  
Key Genes

We aimed to identify key genes associated with prostate cancer using RNA-sequencing (RNA-seq) data. RNA-seq data, including 1 cancer sample and 1 adjacent normal sample, were downloaded from the NCBI SRA database and the differentially expressed genes (DEGs) were identified with the software Cufflinks. Functional enrichment analysis was performed to uncover the biological functions of DEGs. Regulatory information was retrieved from the IPA database and a network was established. A total of 147 DEGs were obtained, including 96 downregulated and 51 upregulated DEGs. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that metabolism and signal transduction were the 2 major functions that were significantly influenced. Moreover, an interaction network was built. In conclusion, a number of DEGs was identified and their roles in the pathogenesis of cancer were supported by previous studies. More studies are necessary to further validate their usefulness in the diagnosis and treatment of prostate cancer.

scholarly journals Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 66 ◽  
Author(s):  
Chuan Zhang ◽  
Mandy Berndt-Paetz ◽  
Jochen Neuhaus
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Cell Movement ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Nodal Metastasis ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Protein Protein Interaction

Bladder cancer (BCa) is one of the most common malignancies and has a relatively poor outcome worldwide. However, the molecular mechanisms and processes of BCa development and progression remain poorly understood. Therefore, the present study aimed to identify candidate genes in the carcinogenesis and progression of BCa. Five GEO datasets and TCGA-BLCA datasets were analyzed by statistical software R, FUNRICH, Cytoscape, and online instruments to identify differentially expressed genes (DEGs), to construct protein‒protein interaction networks (PPIs) and perform functional enrichment analysis and survival analyses. In total, we found 418 DEGs. We found 14 hub genes, and gene ontology (GO) analysis revealed DEG enrichment in networks and pathways related to cell cycle and proliferation, but also in cell movement, receptor signaling, and viral carcinogenesis. Compared with noncancerous tissues, TPM1, CRYAB, and CASQ2 were significantly downregulated in BCa, and the other hub genes were significant upregulated. Furthermore, MAD2L1 and CASQ2 potentially play a pivotal role in lymph nodal metastasis. CRYAB and CASQ2 were both significantly correlated with overall survival (OS) and disease-free survival (DFS). The present study highlights an up to now unrecognized possible role of CASQ2 in cancer (BCa). Furthermore, CRYAB has never been described in BCa, but our study suggests that it may also be a candidate biomarker in BCa.

scholarly journals Upregulated CD58 is associated with clinicopathological characteristics and poor prognosis of patients with pancreatic ductal adenocarcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yalu Zhang ◽  
Qiaofei Liu ◽  
Jingkai Liu ◽  
Quan Liao
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Clinicopathological Characteristics ◽  
Functional Enrichment ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition

Abstract Background CD58 has been demonstrated to be abnormally expressed in multiple hematopoietic malignancies and solid tumors and plays an essential role in tumorigenesis and progression; however, its clinical significance and prognostic value in pancreatic ductal adenocarcinoma (PDAC) remain unknown. Methods Based on diverse online public databases and 81 PDAC samples of tissue microarray-based immunohistochemistry (IHC), we evaluated CD58 expression in PDAC patients and analyzed its association with clinicopathological characteristics, clinical outcomes, and infiltration of immune cells in PDAC. Furthermore, the correlation between CD58 and the cancer stem cell (CSC)-related, epithelial–mesenchymal transition (EMT)-related, and immune-related markers were detected. Besides, the functional enrichment analysis and related pathways were analyzed and visualized. Results CD58 expression was elevated in pancreatitis and PDAC tissues than normal pancreas or adjacent nontumor tissues. The positive cases of CD58 (e.g. more than 50% positive cells) in PDAC account for 95.06% (77/81). Upregulated CD58 in cancer tissues was associated with worse histological grade, larger tumor size, and poorer overall survival and disease-free survival in PDAC patients. Furthermore, Cox multivariate regression analysis revealed that CD58 was an independent prognostic factor in PDAC. CD58 expression was correlated with infiltrations of neutrophils, CD8+ T cells, and dendritic cells (DCs). In addition, correlation gene analysis indicated that CD58 expression was strongly correlated with immune-related, EMT-related, and CSC-related markers. Functional enrichment analysis and KEGG pathway manifested that CD58 might be involved in PDAC initiation and progression. Conclusions CD58 expression is upregulated in PDAC tissues and its high expression is notably related to poor survival of PDAC. Therefore, CD58 may serve as a novel and effective marker for predicting the prognosis of PDAC patients.

Sign in / Sign up

Export Citation Format

Share Document