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Multiple Differential Networks Strategy Reveals Carboplatin and Melphalan-Induced Dynamic Module Changes in
Cui Chen1, Feng-Wei Ma1, Cui-Yun Du1
1Department of Ophthalmology, Yidu Central Hospital of Weifang, Qingzhou, Shandong, China (mainland).
Abstract:
BACKGROUND Retinoblastoma (RB) is the most common malignant tumor of the eye in childhood. The objective of this paper was to investigate carboplatin (CAR)- and melphalan (MEL)-induced dynamic module changes in RB based on multiple (M) differential networks, and to generate systems-level insights into RB progression. MATERIAL AND METHODS To achieve this goal, we constructed M-differential co-expression networks (DCNs), assigned a weight to each edge, and identified seed genes in M DCNs by ranking genes based on their topological features. Starting with seed genes, a module search was performed to explore candidate modules in CAR and MEL condition. M-DMs were detected according to significance evaluations of M-modules, which originated from refinement of candidate modules. Further, we revealed dynamic changes in M-DM activity and connectivity on the basis of significance of Module Connectivity Dynamic Score (MCDS). RESULTS In the present study, M=2, a total of 21 seed genes were obtained. By assessing module search, refinement, and evaluation, we gained 18 2-DMs. Moreover, 3 significant 2-DMs (Module 1, Module 2, and Module 3) with dynamic changes across CAR and MEL condition were determined, and we denoted them as dynamic modules. Module 1 had 27 nodes of which 6 were seed genes and 56 edges. Module 2 was composed of 28 nodes and 54 edges. A total of 28 nodes interacted with 45 edges presented in Module 3. CONCLUSIONS We have identified 3 dynamic modules with changes induced by CAR and MEL in RB, which might give insights in revealing molecular mechanism for RB therapy.
Insights
This study identifies three dynamic gene modules in retinoblastoma (RB) that change with carboplatin (CAR) and melphalan (MEL) treatment, offering new insights into RB molecular mechanisms and therapy. These findings highlight key molecular pathways affected by chemotherapy in eye cancer.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Retinoblastoma (RB) is the most common childhood eye malignancy.
- Understanding RB's molecular progression is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate dynamic gene module alterations in RB induced by carboplatin (CAR) and melphalan (MEL).
- To gain systems-level insights into RB progression and chemotherapy response.
Main Methods:
- Construction of multiple differential co-expression networks (M-DCNs) for RB.
- Identification of seed genes and module searching to detect dynamic modules (M-DMs).
- Analysis of module connectivity and dynamic changes using Module Connectivity Dynamic Score (MCDS).
Main Results:
- Identified 18 two-dimensional modules (2-DMs) and 3 significant dynamic modules (Module 1, Module 2, Module 3).
- These 3 dynamic modules exhibited significant changes under CAR and MEL treatment conditions.
- Detailed network properties for each identified dynamic module (nodes, seed genes, edges).
Conclusions:
- Successfully identified 3 key dynamic modules responsive to CAR and MEL in RB.
- These findings provide potential molecular targets and insights for improving RB therapy.
- The study contributes to understanding chemotherapy-induced molecular changes in retinoblastoma.
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