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Utilizing endoscopic technology to reveal real-time proteomic alterations in response to chemoprevention
Masako Nakanishi1, Antoine Ménoret, Glenn S Belinsky
1Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT, USA.
Abstract:
Cancer chemoprevention approaches use either pharmacological or dietary agents to impede, arrest or reverse the carcinogenic process. Although several agents have shown effectiveness against colon cancer, present intervention strategies provide only partial reduction. In this study, we utilized high-resolution endoscopy to obtain colon tumor biopsy specimens from Apc mutant mice before and after 2-wk sulindac intervention. To acquire information beyond genomics, proteome analysis using the ProteomeLab PF2D platform was implemented to generate 2-D protein expression maps from biopsies. Chromatograms produced common signature profiles between sulindac and nonsulindac treated samples, and contrasting profiles termed "fingerprints". We selected a double peak that appeared in tumor biopsies from sulindac-treated mice. Further analyses using MS sequencing identified this protein as histone H2B. The location of H2B in the 1(st) dimension strongly suggested PTM, consistent with identification of two oxidized methionines. While further studies on sulindac proteomic fingerprints are underway, this study demonstrates the feasibility and advantages of "real-time" proteomic analysis for obtaining information on biomarker discovery and drug activity that would not be revealed by a genetic assay. This approach should be broadly applicable for assessing lesion responsiveness in a wide range of translational and human clinical studies.
Insights
This study used proteomic analysis to identify histone H2B as a biomarker in colon tumors after sulindac treatment. This "real-time" proteomic approach reveals drug activity not seen in genetic assays.
Area of Science:
- Oncology
- Proteomics
- Chemoprevention
Background:
- Chemoprevention strategies aim to prevent or reverse cancer, but current methods offer limited efficacy for colon cancer.
- Sulindac is a non-steroidal anti-inflammatory drug investigated for its chemopreventive properties.
Purpose of the Study:
- To investigate the utility of proteomic analysis for real-time biomarker discovery and drug activity assessment in colon cancer chemoprevention.
- To identify protein expression changes in colon tumors following sulindac intervention.
Main Methods:
- Colon tumor biopsy specimens were collected from Apc mutant mice before and after a 2-week sulindac intervention.
- High-resolution endoscopy was used for biopsy collection.
- Proteome analysis was performed using the ProteomeLab PF2D platform to generate 2-D protein expression maps.
- Mass spectrometry (MS) sequencing was employed for protein identification.
Main Results:
- Proteomic analysis generated distinct "fingerprints" differentiating sulindac-treated and untreated samples.
- A specific protein peak, identified as histone H2B, was consistently found in tumors from sulindac-treated mice.
- Histone H2B exhibited post-translational modifications (PTMs), specifically oxidized methionines, suggesting drug-induced changes.
Conclusions:
- Proteomic analysis provides a feasible and advantageous method for real-time biomarker discovery and assessment of drug activity in cancer research.
- This approach can reveal insights into drug mechanisms and lesion responsiveness that are not obtainable through genetic assays alone.
- The findings support the broad applicability of proteomic fingerprinting in translational and clinical studies for evaluating cancer interventions.
