Cell surface proteomics identifies glucose transporter type 1 and prion protein as candidate biomarkers for colorectal adenoma-to-carcinoma progression
- Meike de Wit1,2,
- Connie R Jimenez2,
- Beatriz Carvalho1,
- Jeroen A M Belien1,
- Pien M Delis-van Diemen1,
- Sandra Mongera1,
- Sander R Piersma2,
- Maindad Vikas3,
- Sanjay Navani3,
- Fredrik Pontén4,
- Gerrit A Meijer1,
- Remond J A Fijneman1
- 1Department of Pathology (Tumor Profiling Unit), VU University Medical Center, Amsterdam, The Netherlands
- 2Department of Medical Oncology (OncoProteomics Laboratory), VU University Medical Center, Amsterdam, The Netherlands
- 3Lab Surg Path, Mumbai, India
- 4Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
- Correspondence to Dr Remond J A Fijneman, Department of Pathology, VU University Medical Center, Rm CCA 1.08, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands;
Contributors 1. Study concept and design. 2. Acquisition of data. 3. Analysis and interpretation of data. 4. Drafting of the manuscript. 5. Critical revision of the manuscript for important intellectual content. 6. Statistical analysis. 7. Obtained funding. 8. Technical or material support. 9. Study supervision. Meike de Wit (1–6), C R Jimenez (1, 3–5, 7, 9), B Carvalho (2, 3, 5), J A M Belien (2, 3, 5), P M Delis-van Diemen (2, 8), S Mongera (2, 3, 8), S R Piersma (2, 3, 5, 8), M Vikas (3), S Navani (3), F Pontén (2, 3, 8), G A Meijer (1, 3–5, 7, 9), R J A Fijneman (1, 3–7, 9).
- Revised 5 July 2011
- Accepted 25 July 2011
- Published Online First 2 September 2011
Background and objective Early detection of colon adenomas at high risk of progression and early-stage colorectal cancer (CRC) is an effective approach to reduce CRC death rates. Current screening methods lack specificity as they detect many adenomas that will never progress to CRC. The authors aimed to identify cell surface protein biomarkers with extracellular domains that could be targeted for molecular imaging and discriminate low-risk adenomas and normal colon from high-risk adenomas and CRC.
Design Cell surface proteins of five CRC cell lines were biotinylated, isolated and analysed by in-depth proteomics using gel electrophoresis and nanoliquid chromatography coupled to tandem mass spectrometry. Differential expression in adenomas and CRCs was based on mRNA expression and verified by immunohistochemical staining of tissue microarrays.
Results In total, 2609 proteins were identified in the cell surface fractions. Of these, 44 proteins were selected as promising cell surface candidate biomarkers for adenoma-to-carcinoma progression based on the following criteria: protein identification in at least four out of five cell lines, a predicted (trans)membrane location and increased mRNA expression in CRCs compared to adenomas. Increased protein expression in high-risk adenomas and CRCs compared to low-risk adenomas was confirmed by immunohistochemistry for glucose transporter type 1 (gene symbol SLC2A1; p<0.00001) and prion protein (gene symbol PRNP; p<0.005).
Conclusion This study revealed glucose transporter type 1, prion protein and 42 other cell surface candidate biomarkers for adenoma-to-carcinoma progression that could potentially serve as targets for emerging molecular imaging modalities like optical imaging, 19F-MRI and positron emission tomography.
- Colorectal cancer
- adenoma-to-carcinoma progression
- tumour markers for molecular imaging
- tumour markers
- colon carcinogenesis
- gastric cancer
- genetic instability
- colonic adenomas
- molecular biology
Funding This work was supported by Philips Healthcare (MdW) and the VUmc–Cancer Center Amsterdam (CRJ and proteomics infrastructure). This study was performed within the framework of CTMM, the Center for Translational Molecular Medicine. DeCoDe project (grant 03O-101).
Competing interests None.
Ethics approval This study was conducted with the approval of the Medical Ethics Review Board of the VU University Medical Center Amsterdam.
Provenance and peer review Not commissioned; externally peer reviewed.