&lt;p&gt;Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma&lt;/p&gt;

Wang, Wei; Xu, Yangchun; Wang, Qiang

doi:10.2147/ott.s277795

Cited by 8 publications

(9 citation statements)

References 56 publications

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“…Mean OS was 97 months for patients with SPARC expression >14.25% compared to 65 months for patients with expression ≤14.25%. These findings are consistent with the literature, in which there is an association between low SPARC expression and a worse prognosis in endometrial carcinoma ( 76 ), colorectal cancer ( 87 , 88 ), and NSCLC ( 89 ). Furthermore, it is described that, depending on the tumor microenvironment, SPARC can act both as a tumor suppressor and as an oncogene ( 76 ).…”

Section: Discussionsupporting

confidence: 93%

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Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions

Baldavira

Prieto²,

Machado-Rugolo³

et al. 2022

Front. Oncol.

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Lung cancer still represents a global health problem, being the main type of tumor responsible for cancer deaths. In this context, the tumor microenvironment, and the extracellular matrix (ECM) pose as extremely relevant. Thus, this study aimed to explore the prognostic value of epithelial-to-mesenchymal transition (EMT), Wnt signaling, and ECM proteins expression in patients with non–small-cell lung carcinoma (NSCLC) with clinical stages I-IIIA. For that, we used 120 tissue sections from patients and evaluated the immunohistochemical, immunofluorescence, and transmission electron microscopy (TEM) to each of these markers. We also used in silico analysis to validate our data. We found a strong expression of E-cadherin and β-catenin, which reflects the differential ECM invasion process. Therefore, we also noticed a strong expression of chondroitin sulfate (CS) and collagens III and V. This suggests that, after EMT, the basal membrane (BM) enhanced the motility of invasive cells. EMT proteins were directly associated with WNT5A, and collagens III and V, which suggests that the WNT pathway drives them. On the other hand, heparan sulfate (HS) was associated with WNT3A and SPARC, while WNT1 was associated with CS. Interestingly, the association between WNT1 and Col IV suggested negative feedback of WNT1 along the BM. In our cohort, WNT3A, WNT5A, heparan sulfate and SPARC played an important role in the Cox regression model, influencing the overall survival (OS) of patients, be it directly or indirectly, with the SPARC expression stratifying the OS into two groups: 97 months for high expression; and 65 for low expression. In conclusion, the present study identified a set of proteins that may play a significant role in predicting the prognosis of NSCLC patients with clinical stages I-IIIA.

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Section: Discussionsupporting

confidence: 93%

“…This is a matricellular glycoprotein that directly participates in the ECM remodeling process, regulating processes, such as metalloproteinase secretion and cell-matrix interactions ( 75 ). Recent studies showed that SPARC favored the migration and invasion of endometrial carcinoma cells in vitro and in vivo ( 76 ).…”

Section: Discussionmentioning

confidence: 99%

Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions

Baldavira

Prieto²,

Machado-Rugolo³

et al. 2022

Front. Oncol.

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“…In endometrial cancer (EC), low SPARC expression is related to aggressive EC phenotype and poor prognosis. In addition, down-regulation of SPARC promotes the EMT process and enhances EC cell proliferation and invasion [ 34 ]. The AKAP13 is an anchor protein found in the Rho signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

A new signature based on alternative polyadenylation for prognostic prediction and therapeutic responses in low-grade glioma

Wang

Zhang

2022

Aging

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Background: Evidence from research supports the significant role of alternative polyadenylation (APA) in the development of cancer. The aim of this study is to explore the prognostic and therapeutic value of APA events for patients with low-grade gliomas (LGG). Methods: The gene expression and APA profiles of patients with low-grade gliomas were obtained from The Cancer Genome Atlas database. All patients were sorted randomly into training and test sets. The prognostic-associated events of alternative splicing were screened by univariate Cox regression. Subsequently, Least Absolute Shrinkage and Selection Operator and multivariate Cox analysis were performed to construct a prognostic signature. The patients were sorted into the high and low-risk groups based on their median risk score. Bioinformatics methods were used to identify genetic variation, pathway activation, immune heterogeneity, and drug response differences between the two groups. Results: A prognostic signature was constructed shown to be capable of accurately predicting prognosis of patients with LGG. Notable variations were observed in the tumor mutation burden and copy number variations between the high-risk and low-risk patients. Besides, the high-risk group had enhanced immune cell abundance and immune checkpoint gene expression. In terms of drug response, we further found that the patients of high-risk group were more sensitive to immunotherapy, but chemotherapy was suggestively more appropriate for the low-risk group patients. Conclusion: Our findings give new insights and methods related to prognosis prediction and treatment methods for LGG patients, and expand the understanding regarding the role of alternative splicing in LGG.

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“…SPARC is a matricellular glycoprotein that modulates the pathologies associated with tumorigenesis. 28 Jiang et al found that the mRNA and protein expression of SPARC was downregulated in JEG-3 cells compared with HTR-8/SVneo cells. 29 Furthermore, miRNAs in cancer were the primary pathway for DEG enrichment.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs

Peng¹,

Zhang²,

Mo³

et al. 2021

OTT

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Objective The aim of the current research was to construct a miRNA-transcription factor (TF)-target gene regulatory network in order to investigate the mechanism underlying choriocarcinoma and to verify the network through the overexpression or silencing of hub miRNAs in vitro. Materials and Methods A mRNA expression dataset and two miRNA expression datasets were analysed to identify differentially expressed genes (DEGs) and miRNAs (DEMs) between normal cells and choriocarcinoma cells. The top 400 upregulated and downregulated DEGs were identified as candidate DEGs, which were then mapped to construct protein–protein interaction (PPI) networks and select hub genes. Moreover, the DGIdb database was utilized to select candidate drugs for hub genes. Moreover, DEM target genes were predicted through the miRWalk2.0 database and overlaid with candidate DEGs to identify the differentially expressed target genes (DETGs). Furthermore, we established miRNA-TF-target gene regulatory networks and performed functional enrichment analysis of hub DEMs. Finally, we transfected mimics or inhibitors of hub DEMs into choriocarcinoma cells and assessed cell proliferation and migration to verify the vital role of hub DEMs in choriocarcinoma. Results A total of 140 DEMs and 400 candidate DEGs were screened from choriocarcinoma cells and normal cells. A PPI network of 400 candidate DEGs was established. Twenty-nine hub genes and 99 associated small molecules were identified to provide potential target drugs for choriocarcinoma treatment. We obtained 70 DETGs of DEMs derived from the intersection between predicted miRNA target genes and candidate DEGs. Subsequently, 3 hub DEMs were selected, and miRNA-TF-target gene regulatory networks containing 4 TFs, 3 TFs and 3 TFs for each network were constructed. The RT-PCR results confirmed that miR-29b-3p was highly expressed and that miR-519c-3p and miR-520a-5p were expressed at low levels in choriocarcinoma cells. The overexpression or silencing results suggested that 3 dysregulated hub DEMs jointly accelerated the proliferation and migration of choriocarcinoma. Conclusion Association of miRNA-TF-target gene regulatory networks may help us explore the underlying mechanism and provide potential targets for the diagnosis and treatment of choriocarcinoma.

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<p>Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma</p>

Cited by 8 publications

References 56 publications

Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions

Modeling extracellular matrix through histo-molecular gradient in NSCLC for clinical decisions

A new signature based on alternative polyadenylation for prognostic prediction and therapeutic responses in low-grade glioma

Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs

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