Candidate genes involved in metastasis of colon cancer identified by integrated analysis.
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ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC6536975 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundColon cancer is one of most malignant cancers around worldwide. Nearly 20% patients were diagnosed at colon cancer with metastasis. However, the lack of understanding regarding its pathogenesis brings difficulties to study it.MethodsIn this study, we acquired high-sequence data from GEO dataset, and performed integrated bioinformatic analysis including differently expressed genes, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis, protein-protein analysis, survival analysis to analyze the development of colon cancer.ResultsBy comparing the colon cancer tissues with normal colon tissues, 109 genes were dysregulated; among them, 83 genes were downregulated and 26 genes were upregulated. Two clusters were founded based on the STRING database and MCODE plugin of cytoscape software. Then, six genes with prognostic value were filtered out in UALCAN website.ConclusionWe found that SPP1, VIP, COL11A1, CA2, ADAM12, INHBA could provide great significant prognostic value for colon cancer.
| S-EPMC6465657 | biostudies-literature
Project description:BackgroundColon adenocarcinoma (COAD) is one of the most common malignancies. To identify candidate genes that may be involved in colon adenocarcinoma development and progression, weighted gene co-expression network analysis (WGCNA) was used to construct gene co-expression networks to explore associations between gene sets and clinical features and to identify candidate biomarkers. Moreover, we intend to make a preliminary exploration on it.MethodsGene expression profiles and clinical information were collected from The Cancer Genome Atlas COAD database for analysis. The gene expression profiles of GSE106582 and GSE110224 were screened from the Gene Expression Omnibus database for verification. WGCNA analysis, functional pathway enrichment analysis, and prognosis analysis were performed on three databases. Target genes were selected from the key genes for experimental verification and research.ResultsKey genes obtained by WGCNA analysis were mainly enriched in key functions and pathways such as drug metabolism, steroid hormones, and retinol metabolism. A total of four prognostic genes were screened out: SELENBP1, NAT2, VSIG2, and CES2. VSIG2 was selected as the target gene for experimental verification, and its encoded protein was found to be mainly expressed in immune cells. Its expression was positively correlated with immune infiltration.ConclusionsVSIG2 was shown to be associated with immune invasion and antigen presentation in COAD, suggesting it plays an important role in COAD development and progression. It could be used as a potential biomarker or therapeutic target for COAD.
| S-EPMC8289327 | biostudies-literature
Project description:Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson's two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates.
| S-EPMC6468873 | biostudies-literature
Project description:BackgroundLentinula edodes is one of the most popular edible mushroom species in the world and contains useful medicinal components, such as lentinan. The light-induced formation of brown film on the vegetative mycelial tissues of L. edodes is an important process for ensuring the quantity and quality of this edible mushroom. To understand the molecular mechanisms underlying this critical developmental process in L. edodes, we characterized the morphological phenotypic changes in a strain, Chamaram, associated with abnormal brown film formation and compared its genome-wide transcriptional features.ResultsIn the present study, we performed genome-wide transcriptome analyses of different vegetative mycelium growth phenotypes, namely, early white, normal brown, and defective dark yellow partial brown films phenotypes which were exposed to different light conditions. The analysis revealed the identification of clusters of genes specific to the light-induced brown film phenotypes. These genes were significantly associated with light sensing via photoreceptors such as FMN- and FAD-bindings, signal transduction by kinases and GPCRs, melanogenesis via activation of tyrosinases, and cell wall degradation by glucanases, chitinases, and laccases, which suggests these processes are involved in the formation of mycelial browning in L. edodes. Interestingly, hydrophobin genes such as SC1 and SC3 exhibited divergent expression levels in the normal and abnormal brown mycelial films, indicating the ability of these genes to act in fruiting body initiation and formation of dikaryotic mycelia. Furthermore, we identified the up-regulation of glycoside hydrolase domain-containing genes in the normal brown film but not in the abnormal film phenotype, suggesting that cell wall degradation in the normal brown film phenotype is crucial in the developmental processes related to the initiation and formation of fruiting bodies.ConclusionsThis study systematically analysed the expression patterns of light-induced browning-related genes in L. edodes. Our findings provide information for further investigations of browning formation mechanisms in L. edodes and a foundation for future L. edodes breeding.
| S-EPMC6368761 | biostudies-literature
Project description:Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated. Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD. Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.
| S-EPMC7645237 | biostudies-literature
Project description:BackgroundPlatycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese, and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable.Principal findingsA total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80%) were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG, and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant.ConclusionThe genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level.
| S-EPMC4871891 | biostudies-literature
Project description:Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non?tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t?tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein?protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM?receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator?activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2?a, baculoviral inhibitor of apoptosis repeat?containing protein 5, cyclin?dependent kinase 1, G2/mitotic?specific cyclin?B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid?body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide potential molecular targets and biomarkers for BC.
| S-EPMC5983982 | biostudies-literature
Project description:Breast cancer is one of the most common malignancies. However, the molecular mechanisms underlying its pathogenesis remain to be elucidated. The present study aimed to identify the potential prognostic marker genes associated with the progression of breast cancer. Weighted gene coexpression network analysis was used to construct free-scale gene coexpression networks, evaluate the associations between the gene sets and clinical features, and identify candidate biomarkers. The gene expression profiles of GSE48213 were selected from the Gene Expression Omnibus database. RNA-seq data and clinical information on breast cancer from The Cancer Genome Atlas were used for validation. Four modules were identified from the gene coexpression network, one of which was found to be significantly associated with patient survival time. The expression status of 28 genes formed the black module (basal); 18 genes, dark red module (claudin-low); nine genes, brown module (luminal), and seven genes, midnight blue module (nonmalignant). These modules were clustered into two groups according to significant difference in survival time between the groups. Therefore, based on betweenness centrality, we identified TXN and ANXA2 in the nonmalignant module, TPM4 and LOXL2 in the luminal module, TPRN and ADCY6 in the claudin-low module, and TUBA1C and CMIP in the basal module as the genes with the highest betweenness, suggesting that they play a central role in information transfer in the network. In the present study, eight candidate biomarkers were identified for further basic and advanced understanding of the molecular pathogenesis of breast cancer by using co-expression network analysis.
| S-EPMC6723760 | biostudies-literature
Project description:BACKGROUND:Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this study were to identify differentially expressed genes in the colon of mice with diet-induced obesity and to select candidate genes as early markers of obesity-associated abnormal cell growth in the colon. METHODS:C57BL/6N mice were fed normal diet (11% fat energy) or high-fat diet (40% fat energy) and were euthanized at different time points. Genome-wide expression profiles of the colon were determined at 2, 4, 8, and 12 weeks. Cluster analysis was performed using expression data of genes showing log2 fold change of ?1 or ?-1 (twofold change), based on time-dependent expression patterns, followed by virtual network analysis. RESULTS:High-fat diet-fed mice showed significant increase in body weight and total visceral fat weight over 12 weeks. Time-course microarray analysis showed that 50, 47, 36, and 411 genes were differentially expressed at 2, 4, 8, and 12 weeks, respectively. Ten cluster profiles representing distinguishable patterns of genes differentially expressed over time were determined. Cluster 4, which consisted of genes showing the most significant alterations in expression in response to high-fat diet over 12 weeks, included Apoa4 (apolipoprotein A-IV), Ppap2b (phosphatidic acid phosphatase type 2B), Cel (carboxyl ester lipase), and Clps (colipase, pancreatic), which interacted strongly with surrounding genes associated with colorectal cancer or obesity. CONCLUSIONS:Our data indicate that Apoa4, Ppap2b, Cel, and Clps are candidate early marker genes associated with obesity-related pathological changes in the colon. Genome-wide analyses performed in the present study provide new insights on selecting novel genes that may be associated with the development of diseases of the colon.
| S-EPMC5120484 | biostudies-literature
Project description:Alzheimer's disease (AD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. Identifying altered neuronal gene expression in AD may provide diagnostic or therapeutic targets for AD. The present study aimed to identify differentially expressed genes (DEGs) and their further association with other biological processes that regulate causative factors for AD. The present study performed an integrated analysis of publicly available gene expression omnibus datasets of AD hippocampi. Gene ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein‑Protein interaction (PPI) network analysis were performed. The present study detected 295 DEGs (109 upregulated and 186 downregulated genes) in hippocampi between AD and control samples by integrating four datasets of gene expression profiles of hippocampi of patients with AD. Respiratory electron transport chain (GO: 0022904; P=1.64x10‑11) was the most significantly enriched GO term among biological processes, while for molecular functions, the most significantly enriched GO term was that of protein binding (GO: 0005515; P=3.03x10‑29), and for cellular components, the most significantly enriched GO term was that of the cytoplasm (GO: 0005737; P=8.67x10‑33). The most significant pathway in the KEGG analysis was oxidative phosphorylation (P=1.61x10‑13). PPI network analysis showed that the significant hub proteins contained β-actin (degree, 268), hepatoma-derived growth factor (degree, 218) and WD repeat‑containing protein 82 (degree, 87). The integrated analysis performed in the present study serves as a basis for identifying novel drug targets to develop improved therapies and interventions for common and devastating neurological diseases such as AD.
| S-EPMC4626122 | biostudies-literature