Dataset Information

Molecular Insights on Post-chemotherapy Retinoblastoma by Microarray Gene Expression Analysis.

ABSTRACT:

Purpose

Management of Retinoblastoma (RB), a pediatric ocular cancer is limited by drug-resistance and drug-dosage related side effects during chemotherapy. Molecular de-regulation in post-chemotherapy RB tumors was investigated.

Materials and methods

cDNA microarray analysis of two post-chemotherapy and one pre-chemotherapy RB tumor tissues was performed, followed by Principle Component Analysis, Gene ontology, Pathway Enrichment analysis and Biological Analysis Network (BAN) modeling. The drug modulation role of two significantly up-regulated genes (p≤0.05) - Ect2 (Epithelial-cell-transforming-sequence-2), and PRAME (preferentially-expressed-Antigen-in-Melanoma) was assessed by qRT-PCR, immunohistochemistry and cell viability assays.

Results

Differential up-regulation of 1672 genes and down-regulation of 2538 genes was observed in RB tissues (relative to normal adult retina), while 1419 genes were commonly de-regulated between pre-chemotherapy and post- chemotherapy RB. Twenty one key gene ontology categories, pathways, biomarkers and phenotype groups harboring 250 differentially expressed genes were dys-regulated (EZH2, NCoR1, MYBL2, RB1, STAMN1, SYK, JAK1/2, STAT1/2, PLK2/4, BIRC5, LAMN1, Ect2, PRAME and ABCC4). Differential molecular expressions of PRAME and Ect2 in RB tumors with and without chemotherapy were analyzed. There was neither up- regulation of MRP1, nor any significant shift in chemotherapeutic IC50, in PRAME over-expressed versus non-transfected RB cells.

Conclusion

Cell cycle regulatory genes were dys-regulated post-chemotherapy. Ect2 gene was expressed in response to chemotherapy-induced stress. PRAME does not contribute to drug resistance in RB, yet its nuclear localization and BAN information, points to its possible regulatory role in RB.

SUBMITTER: Nalini V

PROVIDER: S-EPMC3785389 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Molecular Insights on Post-chemotherapy Retinoblastoma by Microarray Gene Expression Analysis.

Nalini Venkatesan V Segu Ramya R Deepa Perinkulam Ravi PR Khetan Vikas V Vasudevan Madavan M Krishnakumar Subramanian S

Bioinformatics and biology insights 20130918

<h4>Purpose</h4>Management of Retinoblastoma (RB), a pediatric ocular cancer is limited by drug-resistance and drug-dosage related side effects during chemotherapy. Molecular de-regulation in post-chemotherapy RB tumors was investigated.<h4>Materials and methods</h4>cDNA microarray analysis of two post-chemotherapy and one pre-chemotherapy RB tumor tissues was performed, followed by Principle Component Analysis, Gene ontology, Pathway Enrichment analysis and Biological Analysis Network (BAN) mod ...[more]

PMID: 24092970

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Project description:BackgroundRetinoblastoma (RB) is frequently occurring malignant tumors that originate in the retina, and their exact cause and development mechanisms are yet to be fully comprehended. In this study, we identified possible biomarkers for RB and delved into the molecular mechanics linked with such markers.MethodsIn this study GSE110811 and GSE24673 were analyzed. Weighted gene co-expression network analysis (WGCNA) was applied to screen modules and genes associated with RB. By overlapping RB-related module genes with differentially expressed genes (DEGs) between RB and control samples, differentially expressed retinoblastoma genes (DERBGs) were acquired. A gene ontology (GO) enrichment analysis and a kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted to explore the functions of these DERBGs. To study the protein interactions of DERBGs, a protein-protein interaction (PPI) network was constructed. Hub DERBGs were screened using the least absolute shrinkage and selection operator (LASSO) regression analysis, as well as the random forest (RF) algorithm. Additionally, the diagnostic performance of RF and LASSO methods was evaluated using receiver operating characteristic (ROC) curves and single-gene gene set enrichment analysis (GSEA) was conducted to explore the potential molecular mechanisms involved with these Hub DERBGs. In addition, the competing endogenous RNA (ceRNA) regulatory network of Hub DERBGs was constructed.ResultAbout 133 DERBGs were found to be associated with RB. GO and KEGG enrichment analyses revealed that the important pathways of these DERBGs. Furthermore, the PPI network revealed 82 DERBGs interacting with each other. By RF and LASSO methods, PDE8B, ESRRB, and SPRY2 were identified as Hub DERBGs in patients with RB. From the expression assessment of Hub DERBGs, it was found that the levels of expression of PDE8B, ESRRB, and SPRY2 were significantly decreased in the tissues of RB tumors. Secondly, single-gene GSEA revealed a connection between these 3 Hub DERBGs and oocyte meiosis, cell cycle, and spliceosome. Finally, the ceRNA regulatory network revealed that hsa-miR-342-3p, hsa-miR-146b-5p, hsa-miR-665, and hsa-miR-188-5p may play a central role in the disease.ConclusionHub DERBGs may provide new insight into RB diagnosis and treatment based on the understanding of disease pathogenesis.

Project description:BackgroundIntravenous chemotherapy (IVC) and intra-arterial chemotherapy (IAC) have become the primary treatments for retinoblastoma; however, some controversy remains over which method is more effective. We conducted a meta-analysis to compare the clinical efficacy of IVC and IAC.MethodsWe systematically searched literature published on PubMed, Embase, and Cochrane Library up to May 2017. Studies containing either IAC or IVC that reported on efficacy were included. The effects estimate was expressed as a pooled rate with 95% confidence interval (CI), using a fixed-effects or random-effects model.ResultsTwenty-six studies were identified which included 1541 eyes (IAC: 11 trials, 445 eyes; IVC: 16 trials, 1096 eyes). The mean follow-up times were 49.4 months (range, 13.0-105.3 months) for IVC and 21.7 months (range, 8.8-38.7 months) for IAC. For the International Classification of Intraocular Retinoblastoma (ICRB) grading, the overall success rate was higher with IAC than with IVC (75.7% [95%CI: 65.7%-83.6%] vs. 69.5% [95%CI: 51.9%-82.8%], P < 0.001). The globe salvage with IAC was higher than with IVC in group D eyes (79.5% [95%CI: 71.8%-85.4%] vs. 55.1% [95%CI: 45.6%-64.2%], P < 0.001), but not in groups B (95.8% [95%CI: 57.5%-99.7%] vs. 82.5% [95%CI: 58.9%-94.0%], P = 0.163), C (91.3% [95%CI: 65.9%-98.3%] vs. 89.0% [95%CI: 69.0%-96.7%], P = 0.212), and E eyes (51.2% [95%CI: 37.0%-65.2%] vs. 43.2% [95%CI: 18.3%-72.1%], P = 0.578). IAC and IVC were not significantly different regarding the recurrence and metastasis rates (15.0% vs. 15.4%, P = 0.148 and 2.7% vs. 0.6%, P = 0.194, respectively). For Reese-Ellsworth (RE) grading, IAC had a higher globe salvage in groups IV (90.9% [95%CI: 56.0%-98.7%] vs. 66.3% [95%CI: 32.4%-89.0%], P = 0.047) and V eyes (83.2% [95%CI: 72.0%-90.5%] vs. 59.9% [95%CI: 43.1%-74.6%], P = 0.003), but not in group I-III eyes (88.6% [95%CI: 58.3%-97.7%] vs. 88.1% [95%CI: 76.6%-94.4%], P = 0.244). The overall success rate was higher in IAC than in IVC (87.1% [95%CI: 78.1%-92.7%] vs. 77.3% [95%CI: 68.1%-84.4%], P = 0.033).ConclusionsIAC may be superior to IVC for the treatment of retinoblastoma, with a higher overall success rate and higher globe salvage in group D or groups IV and V eyes.

Dataset Information

Molecular Insights on Post-chemotherapy Retinoblastoma by Microarray Gene Expression Analysis.

Purpose

Materials and methods

Results

Conclusion

Publications

Molecular Insights on Post-chemotherapy Retinoblastoma by Microarray Gene Expression Analysis.

Similar Datasets

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