Related Experiment Video
Updated: May 7, 2026
Reconstruct Human Retinoblastoma In Vitro
Published on: October 11, 2022
Molecular Insights on Post-chemotherapy Retinoblastoma by Microarray Gene Expression Analysis
Venkatesan Nalini1, Ramya Segu, Perinkulam Ravi Deepa
1Larsen and Toubro Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai, India. ; Birla Institute of Technology and Science (BITS), Pilani, India.
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.
Insights
Chemotherapy alters gene expression in retinoblastoma (RB), a pediatric eye cancer. While Ect2 responds to treatment stress, PRAME may regulate RB but does not cause drug resistance.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Retinoblastoma (RB) management is challenged by chemotherapy resistance and side effects.
- Understanding molecular changes post-chemotherapy is crucial for improving treatment outcomes.
Purpose of the Study:
- To investigate molecular dysregulation in post-chemotherapy retinoblastoma (RB) tumors.
- To assess the drug modulation role of Ect2 (Epithelial-cell-transforming-sequence-2) and PRAME (preferentially-expressed-Antigen-in-Melanoma) genes.
Main Methods:
- cDNA microarray analysis of RB tumor tissues (pre- and post-chemotherapy).
- Bioinformatic analyses including Principle Component Analysis, Gene Ontology, and Pathway Enrichment.
- Biological Analysis Network (BAN) modeling and validation using qRT-PCR, immunohistochemistry, and cell viability assays.
Main Results:
- Significant differential gene expression observed in RB tissues compared to normal retina.
- 250 differentially expressed genes identified within 21 key gene ontology categories, pathways, and biomarkers.
- Ect2 gene expression increased in response to chemotherapy; PRAME showed no contribution to drug resistance but potential regulatory role.
Conclusions:
- Chemotherapy induces dysregulation of cell cycle regulatory genes in retinoblastoma.
- Ect2 expression is a response to chemotherapy-induced stress.
- PRAME's nuclear localization suggests a regulatory role in RB, independent of drug resistance.
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