scholarly journals Diagnosis and Prognostic Value of SPARC in Gastric Carcinoma: database mining for GCTA

2020 ◽  
Author(s):  
Diqi Ying ◽  
Ding Li ◽  
Xiao Jin

Abstract Gastric carcinoma (GC) remains high incidence and mortality both in developed and developing countries. SPARC is extracellular non-structural matrix glycoprotein. Previous studies were closely associated with bone disease. However, the role of SPARC in GC remains largely unclear. In our study, we explored the diagnosis, prognosis and pathway enrichments value of SPARC in GC. Here, with the data from The Cancer Genome Atlas (TCGA), we used receiver operating characteristic (ROC) curve analysis to estimate the diagnosis value of the SPARC expression, Univariate and multivariate analysis to the prognosis, Gene set enrichment analysis (GSEA) to the signal pathway enrichments. As a result, SPARC expression was significantly higher in the GC tissue samples. Those with high SPARC expression of GC patients were worse prognosis. GSEA shows the gene sets related signal pathways including transforming growth factor (TGF) beta signaling pathway, pathways in cancer, Wnt signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway etc. In brief, those results suggest that SPARC can serve as a potential biomarker for GC in diagnosis and prognosis.

2020 ◽  
Author(s):  
Diqi Ying ◽  
Ding Li ◽  
Xiao Jin

Abstract Gastric carcinoma (GC) remains high incidence and mortality both in developed and developing countries. SPARC is extracellular non-structural matrix glycoprotein. Previous studies were closely associated with bone disease. However, the role of SPARC in GC remains largely unclear. In our study, we explored the diagnosis, prognosis and pathway enrichments value of SPARC in GC. Here, with the data from The Cancer Genome Atlas (TCGA), we used receiver operating characteristic (ROC) curve analysis to estimate the diagnosis value of the SPARC expression, Univariate and multivariate analysis to the prognosis, Gene set enrichment analysis (GSEA) to the signal pathway enrichments. As a result, SPARC expression was significantly higher in the GC tissue samples. Those with high SPARC expression of GC patients were worse prognosis. GSEA shows the gene sets related signal pathways including transforming growth factor (TGF) beta signaling pathway, pathways in cancer, Wnt signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway etc. In brief, those results suggest that SPARC can serve as a potential biomarker for GC in diagnosis and prognosis.


2020 ◽  
Author(s):  
Luqi xue ◽  
E Yang ◽  
Jinhai Gou ◽  
Dan Nie ◽  
Tao Yi ◽  
...  

Abstract Background The pathogenesis and clinical behaviors between solitary uterine leiomyoma (SUL) and multiple uterine leiomyomas (MUL) vary, which lead to the difference in management for childbearing-aged patients. Herein, we aim to find the potential miRNAs involved in the development of SUL and MUL. Results The top 5 differentially expressed miRNAs, Wnt signalling pathway and its two central molecules APC and CTNNB1 were screened out according to microarray analysis and bioinformatics. MiR-142-3p was selected for further exploration. In validation of qRT-PCR, MiR-142-3p was significantly upregulated in SUL, while downregulated in MUL, CTNNB1 and sequencing target AXIN-2 were expressed at higher level in MUL than SUL. Overexpression of MiR-142-3p resulted in lower transcription level of CTNNB1 and AXIN-2, and lower cell proliferation level. Conclusions MiR-142-3p may be involved in the development of SUL and MUL by interacting with CTNNB1 and AXIN-2 through Wnt signaling pathway. MiR-142-3p could serve as a potential biomarker for individualized treatment between SUL and MUL in the future.


Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 767
Author(s):  
Byoung Ha Kim ◽  
Won-Yung Lee ◽  
Tuy An Trinh ◽  
Jae Sung Pyo ◽  
Sooyeun Lee ◽  
...  

Janus kinase 3 (JAK3) inhibitors have been used effectively in the treatment of several cases of alopecia universalis and its variants. Our study aims to evaluate whether the emulsion extract of brevilin A from Centipeda minima (CMX) stimulates hair regrowth in a clinical trial, as a JAK3 inhibitor, combined with network pharmacology-based analysis. CMX showed potent inhibition of JAK3 in a concentration-dependent manner. Significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects. The gene set enrichment analysis showed that the targets of CMX are mainly associated with the JAK-STAT signaling pathway, cytokine–cytokine receptor interactions, and the MAPK signaling pathway. This study suggests that the medicinal herbal extract CMX is useful in the treatment of mild to moderate vertex balding that contribute to the visible improvements in hair growth observed in treated patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Gang Wang ◽  
Dan Sun ◽  
Wenhui Li ◽  
Yan Xin

The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases’ data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.


Author(s):  
Shan Lei ◽  
Zhiwei He ◽  
Tengxiang Chen ◽  
Xingjun Guo ◽  
Zhirui Zeng ◽  
...  

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.


2016 ◽  
Vol 48 (7) ◽  
pp. 455-463 ◽  
Author(s):  
Jing Yu ◽  
Ke He ◽  
Ting Ren ◽  
Yaping Lou ◽  
Ayong Zhao

Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development. The let7 family, miR-10 family, and miR-143 family were abundant in these libraries, and they have been suggested to play a housekeeping role during folliculogenesis. Joint comparisons revealed 23 upregulated and 21 downregulated miRNAs (in at least two comparisons of follicles during brooding and laying, P < 0.1) in the laying stage. Unlike reproduction pathways reported for ovaries, GO and KEGG analysis suggested pathways for cell apoptosis and proliferation, such as the regulation of actin cytoskeleton, endocytosis, axon guidance, pathways in cancer, tight junctions, focal adhesion, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and the Wnt signaling pathway in folliculogenesis. This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Yu Tang ◽  
Xiaolei Ma ◽  
Huayong Zhang ◽  
Zhifeng Gu ◽  
Yayi Hou ◽  
...  

We aimed to compare bone-marrow-derived mesenchymal stem cells (BMMSCs) between systemic lupus erythematosus (SLE) and normal controls by means of cDNA microarray, immunohistochemistry, immunofluorescence, and immunoblotting. Our results showed there were a total of 1, 905 genes which were differentially expressed by BMMSCs derived from SLE patients, of which, 652 genes were upregulated and 1, 253 were downregulated. Gene ontology (GO) analysis showed that the majority of these genes were related to cell cycle and protein binding. Pathway analysis exhibited that differentially regulated signal pathways involved actin cytoskeleton, focal adhesion, tight junction, and TGF-βpathway. The high protein level of BMP-5 and low expression of Id-1 indicated that there might be dysregulation in BMP/TGF-βsignaling pathway. The expression of Id-1 in SLE BMMSCs was reversely correlated with serum TNF-αlevels. The protein level of cyclin E decreased in the cell cycling regulation pathway. Moreover, the MAPK signaling pathway was activated in BMMSCs from SLE patients via phosphorylation of ERK1/2 and SAPK/JNK. The actin distribution pattern of BMMSCs from SLE patients was also found disordered. Our results suggested that there were distinguished differences of BMMSCs between SLE patients and normal controls.


2021 ◽  
Author(s):  
Yuanyuan Tian ◽  
Jiao Zhao ◽  
Ju Huang ◽  
Haiying Zhang ◽  
Fushun Ni ◽  
...  

Abstract Background:Tumor endothelial cells (TECs) play an indispensable role in tumor growth and metastasis. Compared with normal endothelial cells (NECs), TECs exhibit unique phenotypic and functional heterogeneity in terms of metabolism, genetics, and transcriptomics. It is not only the key to coordinate tumor angiogenesis, but also an important factor of immune regulation in the tumor microenvironment. In recent years, the role of TECs in tumor metabolism and invasion has been continuously reported. However, the research on the mechanism behind the complex functions of TECs is still at the basic stage. We use Oxford Nanopore Technology (ONT) three-generation full-length transcriptome sequencing to detect all genetic structural changes in the transcriptome of mouse TECs 2H-11 and mouse NECs SVEC4-10.Results: In Tumor endothelial cells 2H-11,1847genes are up-regulated and 1202 genes are down-regulated. According to the Gene ontology (GO) enrichment analysis of differentially expressed genes (DEGs), we found that different functional trends related to metabolic processes, developmental processes, localization, immune system processes, and locomotion are the main reasons for the differences. DEGs are mainly enriched in signal pathways related to cancer, immunity and metabolism, involving Pathways in cancer,Antigen processing and presentation , Proteoglycans in cancer, Focal adhesion, MAPK signaling pathway ,Protein digestion and absorption,ECM-receptor interaction,PI3K-Akt signaling pathway and Glutathione metabolism. We also obtained the structural variation of transcripts such as alternative splicing, gene fusion, and alternative polyadenylation and accurately quantified the expression of the transcript. Some of our results have been confirmed in other documents. But other data have not been reported yet, which is the focus of our future exploration.Conclusion: We try to use transcriptomics and bioinformatics methods to characterize tumor endothelial cell-related genes and signaling pathways.It could help better understand the molecular mechanisms of tumor endothelial cells involved in tumorigenesis and development. DEGs in key pathways may be potential diagnostic markers or therapeutic targets of TECs. Our data also provide useful genetic resources for improving the genome and transcriptome annotations of TECs and NECs.


2021 ◽  
Author(s):  
Xiaofen Pan ◽  
Xingkui Tang ◽  
Minling Liu ◽  
Xijun Luo ◽  
Mengyuan Zhu ◽  
...  

Abstract BackgroundTumor microenvironment consists of tumor cells, immune cells and other matric components. Tumor infiltration immune cells are associated with prognosis. But all the current prognosis evaluation system dose not take tumor immune cells other matrix component into consideration. In the current study, we aimed to construct a prognosis predictive model based on tumor microenvironment.MethodCIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. Immune cell infiltration (ICI) scores of each patient were determine by principal-component analysis. Patients were divided to high and low ICI score groups. Survival, gene expression and somatic mutation of the two groups were compared.ResultsPatients with no lymph node invasion, no metastasis, T1-2 disease and stage I-II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF β pathway, and WNT signaling pathway were enriched in high ICI score group. Immune-checkpoint genes and immune-activity associated genes were significantly decreased in high ICI score. Patients in high ICI score group had better survival than low ICI score group. Prognostic value of ICI score was independent of TMB.ConclusionICI score might serve as an independent prognostic biomarker in colon cancer.


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