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Updated: Mar 7, 2026
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Identification of differentially expressed proteins in retinoblastoma tumors using mass spectrometry-based
Jasmine Naru1, Ritu Aggarwal2, Ashok Kumar Mohanty3
1Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India; Department of Biochemistry, Panjab University, Chandigarh 160025, India.
Abstract:
In India, retinoblastoma is among the top five childhood cancers. Children mostly present with extraocular extension and high risk features that results in unsatisfactory treatment and low survival rate. In addition, lack of potential therapeutic and prognostic targets is another challenge in the management of retinoblastoma. We studied comparative proteome of retinoblastoma patients (HPV positive and negative (n=4 each) and controls (n=4), in order to identify potential retinoblastoma-specific protein targets. 2D-DIGE coupled MALDI-TOF/TOF mass spectrometry identified 39 unique proteins. Highly deregulated proteins were GFAP,RBP3,APOA1,CRYAA,CRABP1,SAG and TF. Gene ontology (Panther 7.0) revealed majority of proteins to be associated with metabolic processes (26%) and catalytic activity (38%). 8 proteins were significantly upregulated in HPV positive vis-a-vis HPV negative cases. Patient group exhibited 12 upregulated and 18 downregulated proteins compared to controls. Pathway and network analysis (IPA software) revealed CTNNB1 as most significantly regulated signalling pathway in HPV positive than HPV negative retinoblastoma. The trends in transcriptional change of 9 genes were consistent with those at proteomic level. The Western blot analysis confirmed the expression pattern of RBP3,GFAP and CRABP1. We suggest GFAP,RBP3,CRABP1,CRYAAA,APOA1 and SAG as prospective targets that could further be explored as potential candidates in therapy and may further assist in studying the disease mechanism.
Significance:
In this study we evaluated tumor tissue specimens from retinoblastoma patients and identified 39 differentially regulated proteins compared to healthy retina. From these, we propose RBP3, CRABP1, GFAP, CRYAA, APOA1 and SAG as promising proteomic signatures that could further be explored as efficient prognostic and therapeutic targets in retinoblastoma. The present study is not only a contribution to the ongoing endeavour for the discovery of proteomic signatures in retinoblastoma, but, may also act as a starting point for future studies aimed at uncovering novel targets for further therapeutic interventions and improving patient outcomes.
Insights
This study identified 39 unique proteins in retinoblastoma, with GFAP, RBP3, CRABP1, CRYAA, APOA1, and SAG showing promise as potential therapeutic targets for this childhood cancer.
Area of Science:
- Proteomics
- Cancer Biology
- Ophthalmology
Background:
- Retinoblastoma is a leading childhood cancer in India, often presenting with advanced disease and poor outcomes.
- Limited therapeutic and prognostic targets hinder effective management of retinoblastoma.
- Understanding the molecular mechanisms of retinoblastoma is crucial for developing novel treatments.
Purpose of the Study:
- To identify potential retinoblastoma-specific protein targets through comparative proteomic analysis.
- To investigate differences in protein expression between HPV-positive and HPV-negative retinoblastoma.
- To discover novel biomarkers for diagnosis, prognosis, and therapy in retinoblastoma.
Main Methods:
- Comparative proteomic analysis using 2D-DIGE coupled with MALDI-TOF/TOF mass spectrometry.
- Analysis of tumor tissue specimens from retinoblastoma patients and healthy controls.
- Bioinformatic analysis including gene ontology, pathway, and network analysis (IPA software).
Main Results:
- 39 unique proteins were identified as differentially regulated in retinoblastoma.
- Key proteins such as GFAP, RBP3, APOA1, CRYAA, CRABP1, SAG, and TF were found to be highly deregulated.
- Significant differences in protein expression were observed between HPV-positive and HPV-negative retinoblastoma cases, with CTNNB1 identified as a key regulated pathway.
Conclusions:
- GFAP, RBP3, CRABP1, CRYAA, APOA1, and SAG are proposed as promising proteomic signatures for retinoblastoma.
- These identified proteins may serve as potential therapeutic and prognostic targets.
- Further research into these targets could lead to improved therapeutic interventions and patient outcomes in retinoblastoma.
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