Discovering the signature of a lupus-related microRNA profile in the Gene Expression Omnibus repository

Lupus ◽  
2020 ◽  
Vol 29 (11) ◽  
pp. 1321-1335
Author(s):  
Forouzan Omidi ◽  
Sayed Abdolhakim Hosseini ◽  
Abbas Ahmadi ◽  
Kambiz Hassanzadeh ◽  
Shima Rajaei ◽  
...  

Lupus is one of the most prevalent systemic autoimmune diseases. It is a multifactorial disease in which genetic, epigenetic and environmental factors play significant roles. The pathogenesis of lupus is not yet well understood. However, deregulation of microRNAs (miRNAs) – one of the post-transcriptional regulators of genes – can contribute to the development of autoimmune diseases. Over the last two decades, advances in the profiling of miRNA using microarray have received much attention, and it has been demonstrated that miRNAs play a regulatory role in the pathogenesis of lupus. Therefore, dysregulated miRNAs can be considered as promising diagnostic biomarkers for lupus. This article is an overview of lupus-related miRNA profiling studies and arrays in the Gene Expression Omnibus (GEO) database. The aims of our study were to widen current knowledge of known dysregulated miRNAs as potential biomarkers of SLE and to introduce a bioinformatics approach to using microarray data and finding novel miRNA and gene candidates for further study. We identified hsa-miR-4709-5p, hsa-miR-140, hsa-miR-145, hsa-miR-659, hsa-miR-134, hsa-miR-150, hsa-miR-584, hsa-miR-409 and hsa-miR-152 as potential biomarkers by integrated bioinformatics analysis.

2021 ◽  
Author(s):  
Guanlin Zhou ◽  
Yijun Zeng ◽  
Yingmin Luo ◽  
Sheng Guo ◽  
Longyuan Bao ◽  
...  

Abstract Background: The mortality rate of early HBV-related hepatocellular carcinoma (HCC) is increasing annually due to sensitive and readily available diagnostic tools are lacking. This study aims to find such diagnostic biomarkers. Methods: MiR-93-5p was chosen as a candidate biomarker base on the analysis of relevant datasets of Gene Expression Omnibus (GEO). It was subjected to validation using qPCR for the quantification of its expression levels in tissue, plasma and saliva sample sets. Results: miR-93-5p was found to be significantly upregulated in HBV-related HCC tissue. Notably, miR-93-5p in plasma and urine was also significantly increased in patients with early HBV-related HCC. The expression of miR-93-5p was significantly and positively correlated between any two kinds of samples (tissue vs. plasma; tissue vs. urine, plasma vs urine). Moreover, miR-93-5p in plasma and urine reduced significantly over one month after the surgery and returned to normal levels. Finally, ROC analysis showed both plasmatic and urinary miR-39-5p could detect early, advanced and total HBV-relative HCC cases with over 85% of sensitivities and over 93% of specificities.Conclusion: plasma and urine miR-93-5p show great promise as novel and potential biomarkers for early HBV-related HCC.


2018 ◽  
Vol 7 ◽  
pp. e1279
Author(s):  
Mona Zamanian Azodi ◽  
Mostafa Rezaei-Tavirani ◽  
Mohammad Rostami-Nejad ◽  
Majid Rezaei-Tavirani

Background: Bladder cancer (BC) has remained as one of the most challenging issues in medicine. The aim of this study was to investigate the differential network analysis of stages 2 and 4 of BC to better understand the molecular pathology of these states. Materials and Methods: We chose gene expression data of GSE52519 from Gene Expression Omnibus (GEO) database analyzed by the GEO2R online tool. Cytoscape version 3.6.1 and its algorithms are the methods applied for the network construction and investigation of differentially expressed genes (DEG) in these states. Result: Our result revealed that the analysis DEGs provides useful information about a common molecular feature of stages 2 and 4 of BC. Conclusion: Consequently, the network finding revealed that more investigation about stage 2 is required to achieve an effective therapeutic protocol to block the transition from stage 2 to stage 4.[GMJ.2018;7:e1279] 


Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 257 ◽  
Author(s):  
Yitong Zhang ◽  
Joseph Ta-Chien Tseng ◽  
I-Chia Lien ◽  
Fenglan Li ◽  
Wei Wu ◽  
...  

Cancer stem cells (CSCs), characterized by self-renewal and unlimited proliferation, lead to therapeutic resistance in lung cancer. In this study, we aimed to investigate the expressions of stem cell-related genes in lung adenocarcinoma (LUAD). The stemness index based on mRNA expression (mRNAsi) was utilized to analyze LUAD cases in the Cancer Genome Atlas (TCGA). First, mRNAsi was analyzed with differential expressions, survival analysis, clinical stages, and gender in LUADs. Then, the weighted gene co-expression network analysis was performed to discover modules of stemness and key genes. The interplay among the key genes was explored at the transcription and protein levels. The enrichment analysis was performed to annotate the function and pathways of the key genes. The expression levels of key genes were validated in a pan-cancer scale. The pathological stage associated gene expression level and survival probability were also validated. The Gene Expression Omnibus (GEO) database was additionally used for validation. The mRNAsi was significantly upregulated in cancer cases. In general, the mRNAsi score increases according to clinical stages and differs in gender significantly. Lower mRNAsi groups had a better overall survival in major LUADs, within five years. The distinguished modules and key genes were selected according to the correlations to the mRNAsi. Thirteen key genes (CCNB1, BUB1, BUB1B, CDC20, PLK1, TTK, CDC45, ESPL1, CCNA2, MCM6, ORC1, MCM2, and CHEK1) were enriched from the cell cycle Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, relating to cell proliferation Gene Ontology (GO) terms, as well. Eight of the thirteen genes have been reported to be associated with the CSC characteristics. However, all of them have been previously ignored in LUADs. Their expression increased according to the pathological stages of LUAD, and these genes were clearly upregulated in pan-cancers. In the GEO database, only the tumor necrosis factor receptor associated factor-interacting protein (TRAIP) from the blue module was matched with the stemness microarray data. These key genes were found to have strong correlations as a whole, and could be used as therapeutic targets in the treatment of LUAD, by inhibiting the stemness features.


2019 ◽  
Author(s):  
ChenChen Yang ◽  
Aifeng Gong

Abstract Background Gastric cancer (GC) has a high mortality rate in cancer-related deaths worldwide. Here, we identified several vital candidate genes related to gastric cancer development and revealed the potential pathogenic mechanisms using integrated bioinformatics analysis.Methods Two microarray datasets from Gene Expression Omnibus (GEO) database integrated. Limma package was used to analyze differentially expressed genes (DEGs) between GC and matched normal specimens. DAVID was utilized to conduct Gene ontology (GO) and KEGG enrichment analysis. The relative expression of OLFM4, IGF2BP3, CLDN1and MMP1were analyzed based on TCGA database provided by UALCAN. Western blot and quantitative real time PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1and MMP1 in GC tissues and cell lines, respectively.Results We downloaded the expression profiles of GSE103236 and GSE118897 from the Gene Expression Omnibus (GEO) database. Two integrated microarray datasets were used to obtain differentially expressed genes (DEGs), and bioinformatics methods were used for in-depth analysis. After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis, we identified 61 DEGs in common, of which the expression of 34 genes were elevated and 27 genes were decreased. GO analysis displayed that the biological functions of DEGs mainly focused on negative regulation of growth, fatty acid binding, cellular response to zinc ion and calcium-independent cell-cell adhesion. KEGG pathway analysis demonstrated that these DEGs mainly related to the Wnt and tumor signaling pathway. Interestingly, we found 4 genes were most significantly upregulated in the DEGs, which were OLFM4, IGF2BP3, CLDN1 and MMP1.Then, we confirmed the upregulation of these genes in STAD based on sample types. In the final, western blot and qRT-PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1 and MMP1 in GC tissues and cell lines.Conclusion In our study, using integrated bioinformatics to screen DEGs in gastric cancer could benefit us for understanding the pathogenic mechanism underlying gastric cancer progression. Meanwhile, we also identified four significantly upregulated genes in DEGs from both two datasets, which might be used as the biomarkers for early diagnosis and prevention of gastric cancer.


2020 ◽  
Author(s):  
Zheng Li ◽  
Zhijiao Wang ◽  
Yingying Zhou

Abstract Background: Cancer stem cells (CSCs) are associated with the recurrence, metastasis and chemoresistance of epithelial ovarian cancer. Competing endogenous RNAs (CeRNAs) play an important role in maintenance of ovarian cancer stem cell-like cells (OCSCs) characteristics. To construct a ceRNA regulatory network for OCSCs, microarray technology and Gene Expression Omnibus (GEO) database had been used. Human serous epithelial ovarian carcinoma cell line COC1 cells were treated with cisplatin and paclitaxel then maintained in stem cell conditions for 6 days to obtain CD117+/CD133+ cells (OCSCs). We identified the differentially expressed miRNAs (DEMs), lncRNA (DELs) and mRNA (DEGs) between OCSCs and COC1 by microarray and combined them with representative microarray profiles in GEO Database. Results: According to the combination, 28 DEMs were identified at first, and 452 DEGs were obtained combining with the predicted targets of these miRNAs and our mRNA microarray results. Up-regulated DEGs of them were significantly enriched in ‘p53 signaling pathway’, ‘FoxO signaling pathway’ and ‘MicroRNAs in cancer’, whereas down-regulated DEGs were significantly enriched in ‘Adherens junction’ and ‘Hepatitis C’ pathway. 29 transcripts of 17 lncRNAs should be the ceRNAs of 10 of these miRNAs according to bioinformatics predicted results and lncRNA microarray. Finally, we obtained ceRNA network with 10 DEMs, 21 DEGs, and 25 transcripts of 13 DELs which should play an important role in maintenance of OCSCs characteristics. LINC00665-miR-146a-5p-NRP2 should be one of ceRNA pathways of the network. The qPCR results indicated that the expression of miR-146a-5p in OCSCs was lower than that in COC1, and LINC00665 shows the opposite trend. These results were consistent with the results of microarray partially. When LINC00665 expression was up-regulated in COC1, the cell proliferation ability enhanced, apoptosis rate reduced, and the percentage of G2/M phase cells increased. Conclusions: The ceRNA network we constructed may be involved in the stem cell characteristics maintenance of OCSCs and provide directions for further OCSCs research in the future, so as to assist the development and treatment of ovarian cancer.


2021 ◽  
Author(s):  
Jian Zhang ◽  
Zehan Liu ◽  
Shuai Ren ◽  
Zilong Shen ◽  
Kecheng Han ◽  
...  

Abstract Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive bone disorder that is characterized by femoral head collapse and hip joint dysfunction. To elucidate the biomarkers of SONFH, the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. A total of 436 differentially expressed SONFH genes were screened in comparison with non-SONFH genes. Six biological processes and four KEGG pathways were enriched in SONFH by GSEA, and 68 candidate genes that were involved in these pathways were selected for subsequent analysis. Moreover, through an ingenuity pathway analysis, we obtained 10 canonical pathways and 20 molecule function modules related to SONFH, and acquired 121 candidate genes. Furthermore, we identified ACP5, TNF, and MMP8 as the genes most related to SONFH according to the VarElect and MalaCards database. Based on these hub genes, the targeted miRNAs and the lncRNAs were predicted. Finally, the ceRNA network was constructed by using ACP5, TNF, MMP8, seven miRNAs, and 956 candidate lncRNAs. In conclusion, the ACP5, TNF, and MMP8 might be potential biomarkers of SONFH.


2019 ◽  
Author(s):  
Hua Lin

Abstract Background: Myocardial ischemia-reperfusion injury always happened after Off-pump coronary artery bypass graft(OPCABG), and this can not be avoided altogether. In this study, we tried to detect potential genes of sevoflurane-induced myocardial energy metabolism in patients undergoing OPCABG using bioinformatics analysis. Methods: We download and analyze the gene expression profile data from the Gene Expression Omnibus(GEO) database using bioinformatics methods. We downloded the gene expression data from the Gene Expression Omnibus(GEO) database using bioinformatics methods. Gene Ontology(GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were used to analysis the screened differentially expressed genes(DEGs). Then, we established a protein–protein interaction (PPI) network to find hub genes associated with myocardial energy metabolism. Results: Through PPI network, we find ten hub genes, including JUN, EGR1, ATF3, FOSB, JUNB, DUSP1, EGR2, NR4A1, BTG2, NR4A2. Conclusions: In conclusion, the proteins encoded by EGR1,ATF3,c-Fos,Btg2,JunB,DUSP1,NR4A1,BTG2 and NR4A2 were related to cardiac function. ATF3, FOSB, JUNB, DUSP1, NR4A1, NR4A2 are related to apoptosis of cardiomyocytes. The protein encoded by BTG2 is related to hypertrophy. Sevoflurane regulates cell transcription, inflammatory and apoptosis through those hub genes to protect myocardial.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Bingchang Xin ◽  
Yuxiang Lin ◽  
He Tian ◽  
Jia Song ◽  
Liwei Zhang ◽  
...  

Inflammatory reaction of pulp tissue plays a role in the pathogen elimination and tissue repair. The evaluation of severity of pulpitis can serve an instructive function in therapeutic scheme. However, there are many limitations in the traditional evaluation methods for the severity of pulpitis. Based on the Gene Expression Omnibus (GEO) database, our study discovered 843 differentially expressed genes (DEGs) related to pulpitis. Afterwards, we constructed a protein-protein interaction (PPI) network of DEGs and used MCODE plugin to determine the key functional subset. Meanwhile, genes in the key functional subset were subjected to GO and KEGG enrichment analyses. The result showed that genes were mainly enriched in inflammatory reaction-related functions. Next, we screened out intersections of PPI network nodes and pulpitis-related genes. Then, 20 genes were obtained as seed genes. In the PPI network, 50 genes that had the highest correlation with seed genes were screened out using random walk with restart (RWR). Furthermore, 4 pulpitis-related hub genes were obtained from the intersection of the top 50 genes and genes in the key functional subset. Finally, GeneMANIA was utilized to predict genes coexpressed with hub genes, and expression levels of the 4 hub genes in normal and pulpitis groups were analyzed based on GEO data. The result demonstrated that the 4 hub genes were mainly coexpressed with chemokine-related genes and were remarkably upregulated in the pulpitis group. In short, we eventually determined 4 potential biomarkers of pulpitis.


2020 ◽  
Author(s):  
Shimei Li ◽  
Jiyi Yao ◽  
Shen Zhang ◽  
Xinchuan Zhou ◽  
Xinbao Zhao ◽  
...  

Abstract Background Ovarian cancer (OV) is the fifth leading cause of cancer death among females. Growing evidence supports a key role of tumor microenvironment in growth, progress, and metastasis of OV. However, the impacts of gene expression signatures related with OV microenvironment on prognosis have not been well-established . This study aimed to apply ESTIMATE algorithm to extract genes related with tumor microenvironment that predicted poor outcomes in OV patients. Methods The gene expression profile of OV samples were downloaded from The Cancer Genome Atlas (TCGA) database. The immune scores and stromal scores of 469 OV samples were available based on the ESTIMATE algorithm. To better understand impacts of gene expression signatures related with OV microenvironment on prognosis, these samples were categorized based on their ESTIMATE scores into high and low score groups. A different OV cohort from the Gene Expression Omnibus (GEO) database was used for external validation. Results The molecular subtypes in OV patients were correlated with stromal scores, in which the mesenchymal subtype had the highest stromal scores (p < 0.0001). Poor prognosis were found in patients (especially for patients with overall survivals (OS) < 5 years) with higher stromal score (p = 0.0376). 449 differentially expressed genes (DEGs) in stromal scores group were identified and 26 DEGs were significantly associated with poor prognosis in OV patients (p < 0.05). Eventually, 6 genes have further validated to be significantly associated with poor outcomes in 40 patients from a different OV cohort of GEO database (p < 0.05). Conclusion In this study, several genes related with tumor microenvironment that predicted poor prognosis in OV patients were extracted. In addition, some previously overlooked genes could be potential prognostic biomarkers for OV.


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