Predicting response to vascular endothelial growth factor inhibitor and chemotherapy in metastatic colorectal cancer

BMC Cancer

Petra Martin³  Sinead Noonan³  Michael P Mullen²  Caitriona Scaife⁴  Miriam Tosetto³  Blathnaid Nolan³  Kieran Wynne⁴  John Hyland³  Kieran Sheahan³  Giuliano Elia⁴  Diarmuid O’Donoghue³  David Fennelly³  Jacintha O’Sullivan¹ 

[1] Department of Surgery, Trinity Centre for Health Sciences, Institute of Molecular Medicine, St. James’s Hospital, Dublin 8, Ireland

[2] College of Life Sciences, University College Dublin, Dublin 4, Ireland

[3] The Centre for Colorectal Disease, St. Vincent’s University Hospital, Dublin 4, Ireland

[4] Conway Institute, University College Dublin, Dublin 4, Ireland

关键词: Proteomics;    Biomarker;    2D-DIGE;    Bevacizumab;    Colorectal cancer;   

Others  :  1117986
DOI  :  10.1186/1471-2407-14-887

 received in 2014-06-19, accepted in 2014-11-14,  发布年份 2014

【 摘 要 】

Background

Bevacizumab improves progression free survival (PFS) and overall survival (OS) in metastatic colorectal cancer patients however currently there are no biomarkers that predict response to this treatment. The aim of this study was to assess if differential protein expression can differentiate patients who respond to chemotherapy and bevacizumab, and to assess if select proteins correlate with patient survival.

Methods

Pre-treatment serum from patients with metastatic colorectal cancer (mCRC) treated with chemotherapy and bevacizumab were divided into responders and nonresponders based on their progression free survival (PFS). Serum samples underwent immunoaffinity depletion and protein expression was analysed using two-dimensional difference gel electrophoresis (2D-DIGE), followed by LC-MS/MS for protein identification. Validation on selected proteins was performed on serum and tissue samples from a larger cohort of patients using ELISA and immunohistochemistry, respectively (n = 68 and n = 95, respectively).

Results

68 proteins were identified following LC-MS/MS analysis to be differentially expressed between the groups. Three proteins (apolipoprotein E (APOE), angiotensinogen (AGT) and vitamin D binding protein (DBP)) were selected for validation studies. Increasing APOE expression in the stroma was associated with shorter progression free survival (PFS) (p = 0.0001) and overall survival (OS) (p = 0.01), DBP expression (stroma) was associated with shorter OS (p = 0.037). Increasing APOE expression in the epithelium was associated with a longer PFS and OS, and AGT epithelial expression was associated with a longer PFS (all p < .05). Increasing serum AGT concentration was associated with shorter OS (p = 0.009).

Conclusions

APOE, DBP and AGT identified were associated with survival outcomes in mCRC patients treated with chemotherapy and bevacizumab.

【 授权许可】

   
2014 Martin et al.; licensee BioMed Central Ltd.

【 图 表 】

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