Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma.
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SUBMITTER: Lenka G
PROVIDER: S-EPMC5309775 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
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Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma.
Lenka Govinda G Tsai Mong-Hsun MH Lin Hsin-Chieh HC Hsiao Jen-Hao JH Lee Yi-Ching YC Lu Tzu-Pin TP Lee Jang-Ming JM Hsu Chung-Ping CP Lai Liang-Chuan LC Chuang Eric Y EY
Scientific reports 20170215
DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were exami ...[more]
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Project description:BackgroundCircular RNAs (circRNAs) may function as the decoys for microRNAs (miRNAs) or proteins, the templates for translation, and the sources of pseudogene generation. The purpose of this study is to determine the diagnostic circRNAs, which are related to lung adenocarcinoma (LUAD), that adsorb miRNAs on the basis of the competing endogenous RNA (ceRNA) hypothesis.MethodsThe differentially expressed circRNAs (DEcircRNAs) in LUAD were revealed by the microarray data (GSE101586 and GSE101684) that were obtained from the Gene Expression Omnibus (GEO) database. The miRNAs that were targeted by the DEcircRNAs were predicted with the CircInteractome, and the target mRNAs of the miRNAs were found by the miRDB and the TargetScan. The ceRNA network was built by the Cytoscape. The potential biological roles and the regulatory mechanisms of the circRNAs were investigated by the Gene Ontology (GO) enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The expression of the host genes of circRNAs was examined by the Ualcan. The survival analysis was performed by the Kaplan-Meier plotter.ResultsIn comparison with normal lung tissues, LUAD tissues contained 7 overlapping cancer-specific DEcircRNAs with 294 miRNA response elements (MREs). Among the 7 DEcircRNAs, 3 circRNAs (hsa_circ_0072088, hsa_circ_0003528, and hsa_circ_0008274) were upregulated and 4 circRNAs (hsa_circ_0003162, hsa_circ_0029426, hsa_circ_0049271, and hsa_circ_0043256) were downregulated. A circRNA-miRNA-mRNA regulatory network, which included 33 differentially expressed miRNAs (DEmiRNAs) and 2007 differentially expressed mRNAs (DEmRNAs), was constructed. These mRNAs were enriched in the biological function of cell-cell adhesion, response to hypoxia, and stem cell differentiation and were involved in the PI3K-Akt signaling, HIF-1 signaling, and cAMP signaling pathways.ConclusionOur results indicated that 7 DEcircRNAs could have diagnostic value for LUAD. Additionally, the circRNAs-mediated ceRNA network might provide a novel perspective into unraveling the pathogenesis and progression of LUAD.
| S-EPMC8448594 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) post-transcriptionally regulate a variety of genes involved in eukaryotic cell growth, development, metabolism and other biological processes, and numerous miRNAs are implicated in the initiation and progression of cancer. Enzootic nasal adenocarcinoma (ENA), an epithelial tumor induced in goats and sheep by enzootic nasal tumor virus (ENTV), is a chronic, progressive, contact transmitted disease.MethodsIn this work, small RNA Illumina high-throughput sequencing was used to construct a goat nasal miRNA library. This study aimed to identify novel and differentially expressed miRNAs in the tumor and para-carcinoma nasal tissues of Nanjiang yellow goats with ENA.ResultsFour hundred six known miRNAs and 29 novel miRNAs were identified. A total of 116 miRNAs were significantly differentially expressed in para-carcinoma nasal tissues and ENA (54 downregulated; 60 upregulated; two only expressed in control group); Target gene prediction and functional analysis revealed that 6176 non-redundancy target genes, 1792 significant GO and 97 significant KEGG pathway for 121 miRNAs (116 significant expression miRNAs and five star sequence) were predicted. GO and KEGG pathway analysis revealed the majority of target genes in ENA are involved in cell proliferation, signal transduction and other processes associated with cancer.ConclusionsThis is the first large-scale identification of miRNAs in Capra hircus ENA and provides a theoretical basis for investigating the complicated miRNA-mediated regulatory networks involved in the pathogenesis and progression of ENA.
| S-EPMC5101819 | biostudies-literature
Project description:Lung cancer is a heterogeneous disease with high mortality rate globally. Lung adenocarcinoma (ADC) is the most common histological subtype of lung cancer. Multiple studies indicate that lncRNAs emerge as a novel class of critical regulators of cancer. However, the expression of lncRNAs has not been comprehensively surveyed in ADC at a genome-wide scale. Herein we examined landscapes of the lncRNAs and their potential target genes in an integrative fashion in ADC. The differences expression level of lncRNAs and mRNA were determined by microarray. qRT-PCR was performed to validate the lncRNAs expression level in a cohort of 42 tumor tissues and adjacent normal lung tissues. R and Bioconductor were used for data analysis. TF-lncRNAs-gene networks were generated by Cytoscape software. A total of 3045 lncRNAs were differentially expressed between tumor and normal tissues (1048 up and 1997 down). The qRT-PCR of 9 lncRNAs results showed that the expression patterns of these lncRNAs were consistent with the microarray data. Meanwhile, we find NONHSAT077036 expression was associated with N classification and clinical stage. Further, we analyzed the potential co-regulatory relationship between the lncRNAs and target genes using the ‘cis’ and ‘trans’ model. In the 25 related transcription factors (TFs), our analysis in TCGA database found that patients with lower expression of POU2F2 and higher expression of TRIM28 had a shorter overall survival time, suggesting that POU2F2 and TRIM28 could be biomarkers for poor prognosis of ADC. Hence, “POU2F2-lncRNAs” “TRIM28-lncRNAs” two element networks and “POU2F2-lncRNAs-mRNAs” “TRIM28-lncRNAs-mRNAs” there element relationship tables were generated.
2017-02-01 | GSE85716 | GEO
Project description:Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based biomarkers of gastric cancer have the potential to improve diagnosis and monitoring of these tumors. Proteins that show altered levels in the circulation of gastric cancer patients could prove useful as putative biomarkers. We used an iTRAQ-based quantitative proteomic approach to identify proteins that show altered levels in the sera of patients with gastric cancer. Our study resulted in identification of 643 proteins, of which 48 proteins showed increased levels and 11 proteins showed decreased levels in serum from gastric cancer patients compared to age and sex matched healthy controls. Proteins that showed increased expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu-Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients.Biological significanceGastric cancer is a highly aggressive cancer associated with high mortality. Serum-based biomarkers are of considerable interest in diagnosis and monitoring of various diseases including cancers. Gastric cancer is often diagnosed at advanced stages resulting in poor prognosis and high mortality. Pathological diagnosis using biopsy specimens remains the gold standard for diagnosis of gastric cancer. Serum-based biomarkers are of considerable importance as they are minimally invasive. In this study, we carried out quantitative proteomic profiling of serum from gastric cancer patients to identify proteins that show altered levels in gastric cancer patients. We identified more than 50 proteins that showed altered levels in gastric cancer patient sera. Validation in a large cohort of well classified patient samples would prove useful in identifying novel blood based biomarkers for gastric cancers. This article is part of a Special Issue entitled: Proteomics in India.
| S-EPMC4618463 | biostudies-literature
Project description:OBJECTIVE:To analyze the differentially expressed genes (DEGs) between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) with bioinformatics analysis and search for potential biomarkers for clinical diagnosis of nonsmall cell lung cancer (NSCLC). METHODS:The gene expression profiling datasets of LUAD and LUSC were acquired. The transcriptome differences between LUAD and LUSC were identified using R language processing and t-test analysis. The differential expressions of the genes were shown by Venn diagram. The DEGs identified by GEO2R were analyzed with DAVID and Ingenuity Pathway Analysis (IPA) to identify the signaling pathways and biomarkers that could be used for differential diagnosis of LUAD and LUSC. The TCGA data and the biomarker expression data from clinical lung cancer samples were used to verify the differential expressions of the Osteoarthritis pathway and LXR/RXR between LUAD and LUSC. We further examined the differential expressions of miR-181 and its two target genes, WNT5A and MBD2, in 23 clinical specimens of lung squamous cell carcinoma and the paired adjacent tissues. RESULTS:GEO data analysis identified 851 DEGs (including 276 up-regulated and 575 down-regulated genes) in LUAD and 885 DEGs (including 406 up-regulated and 479 down-regulated genes) in LUSC. DAVID and IPA analysis revealed that leukocyte migration and inflammatory responses were more abundant in LUAD than in LUSC. Osteoarthritis pathway was inhibited in LUAD and activated in LUSC. IPA analysis showed that transcription factors (GATA4, RELA, YBX1, TP63 and MBD2), cytokines (WNT5A and IL1A) and microRNAs (miR-34a, miR-181b and miR-15a) differed significantly between LUAD and LUSC. miR-34a with IL-1A, miR-15a with YBX1, and miR-181b with WNT5A and MBD2 could serve as the paired microRNA and mRNA targets for differential diagnosis of NSCLC subtypes. Analysis of the clinical samples showed an increased expression of miR-181b-5p and the down-regulation of WNT5A, which could be used as molecular markers for the diagnosis of LUSC. CONCLUSIONS:Through transcriptome analysis, we identified candidate genes, paired microRNAs and pathways for differentiating LUAD and LUSC, and they can provide novel differential diagnosis and therapeutic strategies for LUAD and LUSC.
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Project description:BackgroundLong noncoding RNAs (lncRNAs) could function as competitive endogenous RNAs (ceRNAs) to competitively adsorb microRNAs (miRNAs), thereby regulating the expression of their target protein-coding mRNAs. In this study, we aim to identify more effective diagnostic and prognostic markers for lung adenocarcinoma (LUAD).MethodsWe obtained differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) for LUAD by using The Cancer Genomes Atlas (TCGA) portal. Weighted gene coexpression network analysis (WGCNA) was performed to unveil core gene modules associated with LUAD. The Cox proportional hazards model was performed to determine the prognostic significance of DElncRNAs. The diagnostic and prognostic significance of DElncRNAs was further verified based on the receiver operating characteristic curve (ROC). Cytoscape was used to construct the ceRNA networks comprising the lncRNAs-miRNAs-mRNAs axis based on the correlation obtained from the miRcode, miRDB, and TargetScan.ResultsCompared with normal lung tissues, 2355 DElncRNAs, 820 DEmiRNAs, and 17289 DEmRNAs were identified in LUAD tissues. We generated 8 WGCNA core modules in the lncRNAs coexpression network, 5 modules in the miRNAs, and 12 modules in the mRNAs coexpression network, respectively. One lncRNA module (blue) consisting of 441 lncRNAs, two miRNA modules (blue and turquoise) containing 563 miRNAs, and one mRNA module (turquoise), which consisted of 15162 mRNAs, were mostly significantly related to LUAD status. Furthermore, 67 DEmRNAs were found to be tumor-associated as well as the target genes of the DElncRNAs-DEmiRNAs axis. Survival analyses showed that 6 lncRNAs (LINC01447, WWC2-AS2, OGFRP1, LINC00942, LINC01168, and AC005863.1) were significantly correlated with the prognosis of LUAD patients. Ultimately, the potential ceRNA networks including 6 DElncRNAs, 4 DEmiRNAs, and 22 DEmRNAs were constructed.ConclusionOur study indicated that 6 DElncRNAs had the possibilities as diagnostic and prognostic biomarkers for LUAD. The lncRNA-mediated ceRNA networks might provide novel insights into the molecular mechanisms of LUAD progression.
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Project description:BackgroundTo understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes.MethodsTwo cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression.ResultsTwo libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro.ConclusionsThe two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer.
| S-EPMC3567939 | biostudies-literature
Project description:Purpose:Colon adenocarcinoma (COAD) is the third most common malignancy globally and is further categorized as left colon adenocarcinoma (LCOAD) or right colon adenocarcinoma (RCOAD) depending on the location of the primary tumor. The therapeutic outcome and long-term prognosis for patients with COAD are less than satisfactory, and this may be associated with tumor location. Therefore, it is important to investigate the genetic differences in COAD at different sites. Patients and Methods. Public data associated with COAD were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software (version 3.5.3), and functional annotation of DEGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction network was constructed, hub genes were identified and analyzed, and data mining using Gene Expression Profiling Interactive Analysis (GEPIA) was conducted. Results:A total of 286 DEGs were identified between LCOAD and RCOAD. Additionally, 10 hub genes associated with COAD at different locations were screened, namely, CDKN2A, IGF1R, MDM2, SMAD3, SLC2A1, GRM5, PLCB4, FGFR1, UBE2V2, and TNFRSF10B. The expression of cyclin-dependent kinase inhibitor 2A (CDKN2A) and solute carrier family 2 member 1 (SLC2A1) was significantly associated with pathological stage (P < 0.05). COAD patients with high expression levels of CDKN2A exhibited poorer overall survival (OS) times than those with low expression levels (P < 0.05). Conclusion:CDKN2A expression was significantly different between LCOAD and RCOAD and was closely related to the prognosis of COAD. It is of great value for further understanding of the pathogenesis of LCOAD and RCOAD.
| S-EPMC7201700 | biostudies-literature
Project description:Enzootic nasal adenocarcinoma (ENA), an epithelial tumor induced in goats and sheep by enzootic nasal tumor virus (ENTV), is a chronic, progressive, contact sexually transmitted disease. This study aimed to identify novel and differentially expressed miRNAs in the tumor and para-carcinoma nasal tissues of Nanjiang yellow goats with ENA. Small RNA Illumina high-throughput sequencing was used to construct a goat nasal miRNA library; 406 known miRNAs and 29 novel miRNAs were identified. A total of 116 miRNAs were significantly differentially expressed in para-carcinoma nasal tissues and ENA (54 downregulated; 60 upregulated; 2 only expressed in control group); Target gene prediction and functional analysis revealed that 6176 non-redundancy target genes, 1792 significant GO and 97 significant KEGG pathway for 121 miRNAs (116 significant expression miRNAs and 5 star sequence) were predicted. GO and KEGG pathway analysis revealed the majority of target genes in ENA are involved in cell proliferation, signal transduction and other processes associated with cancer. This is the first large-scale identification of miRNAs in Capra hircus ENA and provides a theoretical basis for investigating the complicated miRNA-mediated regulatory networks involved in the pathogenesis and progression of ENA.
2016-01-25 | GSE65305 | GEO
Project description:Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It's imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.
| S-EPMC8100660 | biostudies-literature