Comprehensive Analysis of the Prognostic Significance of Hsa-miR-100-5p and Its Related Gene Signature in Stomach Adenocarcinoma.
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ABSTRACT:
SUBMITTER: Wang G
PROVIDER: S-EPMC8484799 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As a dominant type of gastric cancer, stomach adenocarcinoma (STAD) is characterized by high morbidity and mortality rates. Anoikis factors participate in tumor metastasis and invasion. This study was designed to identify prognostic risk factors in anoikis-related long non-coding RNAs (lncRNAs) for STAD. First, with STAD expression datasets and anoikis-related gene sets downloaded from public databases, anoikis-related prognostic lncRNA signatures (AC091057.1, ADAMTS9.AS1, AC090825.1, AC084880.3, EMX2OS, HHIP.AS1, AC016583.2, EDIL3.DT, DIRC1, LINC01614, and AC103702.2) were screened by Cox regression to establish a prognostic risk model. Kaplan-Meier and receiver operating characteristic curves were used to evaluate the survival status of patients and verify predictive accuracy of the model. Besides, risk score could be an independent prognostic factor to assess the prognosis of STAD patients. Nomograms of the prognostic model that combined clinical information and risk score could effectively predict survival of STAD patients, as validated by calibration curve. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed for differentially expressed genes (DEGs) in high- and low-risk groups. These DEGs were related to neurotransmitter transmission, signal transmission, and endocytosis. Moreover, we analyzed immune status of different risk groups and found that STAD patients in low-risk group were more sensitive to immunotherapy. A prognostic risk assessment model for STAD using anoikis-related lncRNA genes was constructed here, which was proven to have high predictive accuracy and thus could offer a reference for prognostic evaluation and clinical treatment of STAD patients.
| S-EPMC10259301 | biostudies-literature
Project description:BackgroundStomach adenocarcinoma (STAD) is a leading cause of cancer deaths, but its molecular and prognostic characteristics has never been fully illustrated.AimTo describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures.MethodsWe describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene (EMRG) expression profiles.ResultsOn the basis of 86 EMRGs that were significantly associated to patients' progression-free survival (PFS), we propose a molecular classification dividing gastric cancer into two subtypes: Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process. Compared with patients with low-risk score, patients with high-risk score had shorter overall survival. Furthermore, calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures. According to gene set enrichment analysis, gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway.ConclusionIdentification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.
| S-EPMC8919002 | biostudies-literature
Project description:BackgroundThe circular RNA (circRNA) plays a vital role in the pathogenesis of tumors as a competitive endogenous RNA (ceRNA). Given the high aggressiveness and fatality rate of glioblastoma (GBM) as well as poor prognosis, it is necessary to construct a circRNA-related ceRNA network for further studies on the mechanism of GBM and identify possible biomarkers as well as therapeutic drugs.MethodsThree datasets from the gene expression omnibus (GEO) database were downloaded to distinguish differential circRNAs, microRNAs, and messenger RNAs respectively in GBM. With the help of GEPIA2, circBank, CSCD, TargetScan, miRDB, and miRTarBase databases, we established a circRNAs-related ceRNA network in GBM. Functional enrichments were employed to profile the most relevant mRNAs to indirectly clarify the mechanisms of the ceRNA network. Based on the expression profile data and survival information of GBM patients from the GEO and the cancer genome atlas (TCGA) databases, we performed survival analysis to select prognostic mRNAs and constructed a novel circRNA-miRNA-mRNA central regulatory subnetwork. The DGIdb database was used to find potential drug-gene interactions.ResultsThe datasets obtained from the GEO and TCGA databases were analyzed, and 504 differentially expressed mRNAs (DEmRNAs), 71 differentially expressed microRNAs (DEmiRNAs), and 270 differentially expressed circRNAs (DEcircRNAs) were screened out. The novel ceRNA regulatory network included 22 circRNAs, 11 miRNAs, and 15 mRNAs. FZD1 and KLF10 were significantly correlated with the overall survival rate of patients with GBM (P < 0.05). The final survival subnetwork contained six circRNAs, two miRNAs, and two mRNAs. Two small-molecule compounds and one antibody could be used as therapeutic drugs for GBM. Interestingly, the Wnt signaling pathway appeared in both KEGG and GO functional terms.ConclusionsResults of this study demonstrate that FZD1 and KLF10 may exert regulatory functions in GBM, and the ceRNA-mediated network could be a therapeutic strategy for GBM.
| S-EPMC9909915 | biostudies-literature
Project description:BackgroundStomach adenocarcinoma (STAD) is a major type of gastric cancer with high morbidity and mortality. NPRL2, a candidate cancer suppressor gene, has been shown to have anti-cancer effects in various types of cancers. Therefore, comprehensive analyses of NPRL2 in STAD may provide a potential prognostic marker and clinical target for the management of gastric cancer.MethodsGenomic expression and methylation were analysed based on data from the Human Protein Atlas, Gene Expression Omnibus and Oncomine database. Survival analyses were conducted with the Kaplan-Meier method, using data from The Cancer Genome Atlas database. Immune correlation analyses and prediction of response to immunotherapy were performed using the online Immune Cell Abundance Identifier. Co-expression analyses, functional clustering analyses and construction of a prognostic risk model were conducted in R, with the clinical covariates balanced by the inverse probability treatment weighting method.ResultsNPRL2 was abnormally downregulated in STAD (P<0.05). Survival analysis highlighted a positive association between the expression of NPRL2 and clinical outcomes for patients (P<0.05). Based on co-expression analyses, we found that NPRL2 may be involved in epithelial-mesenchymal transition, gastric cancer stem cells, and responsiveness to chemotherapeutic agents in STAD (P<0.05). Furthermore, functional clustering analysis revealed that NPRL2 was involved in the mTOR signalling pathway, autophagy, and the amino acid starvation response (adjust P<0.05). In addition, NPRL2 was negatively associated with tumour-infiltrating immune cells while positively associated with immunotherapeutic biomarkers in STAD (P<0.05). Meanwhile, patients with high NPRL2 expression were predicted to have a better response to immunotherapy (P<0.05). Finally, a prognostic model constructed based on NPRL2-related genes could predict the prognosis of STAD patients (AUC =0.641), and the risk score was an independent prognostic factor for STAD patients (HR =4.855, 95% CI: 2.683-8.785, P<0.001).ConclusionsThe present study provided a comprehensive analysis of the role and potential mechanisms of NPRL2 in STAD, suggesting that NPRL2 is a potential biomarker for the survival and prediction of immunotherapy response in STAD.
| S-EPMC9459220 | biostudies-literature
Project description:BackgroundGastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients.Patients and methodsA total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR.ResultsWe have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-β, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion.ConclusionOur results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.
| S-EPMC3388997 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) as the subtype of non-coding RNAs are revealed to be crucial players in cellular activities. It has been reported that miR-3619-5p functions as a tumor inhibitor in several cancers. However, the connection between miR-3619-5p and stomach adenocarcinoma (STAD) remains to be discovered.Aim of the studyThe purpose of the study is to figure out the role and molecular regulation mechanism of miR-3619-5p in STAD.MethodsThe expression of miR-3619-5p was evaluated via qRT-PCR analysis. Gain-of-function experiments demonstrated the effects of miR-3619-5p on cellular functions. The upper-stream transcription factor STAT4 and downstream target gene TBC1D10B of miR-3619-5p were identified by bioinformatic analysis. The binding and interaction between the indicated molecules were verified by RNA pull-down and luciferase reporter assays.ResultsThe expression of miR-3619-5p was prominently down-regulated in STAD cells and tissues. MiR-3619-5p suppresses cell proliferation, migration, invasion and tumor growth in STAD. Further, STAT4 bound with miR-3619-5p promoter and inhibited its transcription. MiR-3619-5p was also recognized to modulate STAD progression through the regulation of downstream target gene TBC1D10B.ConclusionSTAT4-mediated miR-3619-5p controls STAD carcinogenesis and progression through modulating TBC1D10B expression, which may provide a novel insight for researching the STAD-related molecular mechanism.
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Project description:The prognostic value and molecular mechanism of microRNA-100-5p (miR-100-5p) in hepatocellular carcinoma (HCC) are still unclear. To explore the prognostic value and the mechanism of miR-100-5p in HCC, the present study analyzed the results of 18 previous studies and bioinformatic datasets. The clinical significance of miR-100-5p and its targets in HCC were investigated using The Cancer Genome Atlas and the Gene Expression Omnibus, as well as relevant literature. In total, 12 online tools were used to predict the target genes of miR-100-5p. Bioinformatics analysis and Spearman correlation analysis were performed, and genomic alterations of the hub genes were evaluated. A meta-analysis with 1,258 samples revealed that miR-100-5p was significantly downregulated in HCC [standard mean difference (SMD), -0.94; 95% confidence interval (CI), -1.14 to -0.74; I2, 35.2%]. Lower miR-100-5p expression was associated with poorer clinical characteristics and a poorer prognosis for patients with HCC. Additionally, bioinformatics analysis revealed that the 'regulation of transcription', 'chromatin remodeling complex', 'transcription regulator activity', 'pathways in cancer' and 'heparan sulfate biosynthesis' were the most enriched terms. Furthermore, expression of histone deacetylase (HDAC)2, HDAC3, SHC-transforming protein 1 (SHC1), Ras-related protein Rac1 (RAC1) and E3 ubiquitin-protein ligase CBL (CBL) was negatively correlated with miR-100-5p expression. Among these, upregulated HDAC2 [hazard ratio (HR), 1.910; 95% CI, 1.309-2.787; P=0.0007], HDAC3 (HR, 1.474; 95% CI, 1.012-2.146; P=0.0435), SHC1 (HR, 1.52; 95% CI, 1.043-2.215; P=0.0281) and RAC1 (HR, 1.817; 95% CI, 1.248-2.645; P=0.0022) were associated with shorter survival. Alterations in HDAC2, SHC1, RAC1 and IGF1R were linked with a poorer outcome for HCC, and alternative splicing of SHC and RAC1 were significantly decreased and increased in HCC, respectively. In summary, the downregulation of miR-100-5p may be involved in the progression and prognosis of HCC. The upregulation of HDAC2, HDAC3, SHC1 and RAC1 may indicate a poorer survival rate for patients with HCC. Thus, miR-100-5p and these 4 potential target genes may provide novel therapeutic targets and prognostic predictors for patients with HCC.
| S-EPMC6865135 | biostudies-literature
Project description:BackgroundGestational diabetes mellitus (GDM) is pregnancy-related diabetes with vital risks for both mother and the fetus. Molecular studies represent one of the popular approaches for investigating mechanisms associated with the disease nature. One of which is through interaction network analysis via Cytoscape V. 3.6.1.MethodsIn this study, the microRNA (miRNA) expression array of GSE98043 from gene expression omnibus (GEO) database was retrieved and screened. We identified 12 differentially expressed (DE) miRNAs (P ≤ 0.05) and nine target hub-bottleneck genes (disease score > 1) for GDM based on miRNA-target interactions created via plugin ClueGO + Cluepedia + STRING.ResultsMiRNA-target information showed that the miRNAs are mostly up-regulated and hsa-miR-145-5p and hsa-miR-875-5p targets the most genes. Among target genes, IL6, GCG, APOB, and ALB have the highest associations with DE-miRNAs. Gene ontology analysis based on biological processes identification via ClueGO + CluePedia, in addition, showed that target hub-bottlenecks are mainly related to metabolism functions and any changes in this regulatory network could impose fundamental alterations in these processes.ConclusionsIt can be concluded that via these introduced miRNAs and their targets, the molecular tests for diagnosis and treatment of GDM can be improved after applying validation approaches.
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Project description:Emerging research indicates that circRNAs serve a crucial role in occurrence and development of cancers. This study aimed to uncover the biological role of hsa_circ_0000519 in the progression of LUAD (lung adenocarcinoma). hsa_circ_0000519 was identified by bioinformatic analysis, and its differential expression was validated in LUAD tissues and cell lines. CCK8, colony formation, wound healing, transwell assays, and xenograft tumor models were used to observe the biological functions of hsa_circ_0000519. FISH, RIP, dual luciferase reporter assays, and recovery experiments were implemented to explore the underlying mechanisms of hsa_circ_0000519. hsa_circ_0000519 was significantly upregulated in LUAD tissues and cell lines. The expression of hsa_circ_0000519 was positively correlated with T grade and TNM stage in patients with LUAD. Downregulation of hsa_circ_0000519 remarkably reduced cell proliferation, migration, invasion in vitro, and tumor growth in vivo. Mechanistic investigation demonstrated that hsa_circ_0000519 directly sponged hsa-miR-1296-5p to reduce its repressive impact on DARS as well as activate the PI3K/AKT/mTOR signaling pathway. The malignant phenotypes of LUAD cells induced by upregulation of hsa_circ_0000519 could be rescued by hsa-miR-1296-5p overexpression or knockdown of DARS. In conclusion, hsa_circ_0000519 promotes LUAD progression through the hsa-miR-1296-5p/DARS axis and may be expected as a novel biomarker and therapeutic for LUAD.
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Project description:Colorectal cancer (CRC) is one of the most common gastrointestinal cancers in the world, and its incidence is increasing all over the world including China. In recent years, research data show that some miRNAs are differentially expressed in cancer tissues, and their expression is closely contributed with the prognosis of CRC. Microarray technology was used, and 179 miRNAs were screened out with significantly altered expression in CRC tissues compared with adjacent tissues. The expression of mir-145-5p in tumor tissues was 3.48 times lower than that in normal tissues. Using bioinformatics technology and network resource prediction, we found that mir-145-5p had a potential target gene relationship with msln gene. Then, qRT-PCR was used to validate the expression level of mir-145-5p and msln mRNA in CRC and paracancerous tissues. The results showed that msln mRNA was higher than in normal tissues, while mir-145-5p was lower, with statistically significant difference (P < 0.01, n = 3). Furthermore, the expression of msln protein in CRC and normal colorectal tissues was detected by protein mass spectrometry (MRM) (n = 3) and immunohistochemistry in a total case of 30 colorectal cancer tissues and normal tissues. Result showed that the positive expression of msln in CRC was higher than that in normal colorectal tissues, 1.38e-6 and 1.89e-6, respectively (P < 0.01, n = 3). Furthermore, in 48 h RTCA real-time monitoring experiment, mir-145-5p showed inhibitory effect on the proliferation of colo320 cells stimulated by msln. This study demonstrated that msln is a target gene of mir-145-5p in CRC. Besides, mir-145-5p negatively regulates the proliferation of CRC colo320 cells through downregulating msln gene expression in CRC colo320 cells.
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