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

Martin P, Noonan S, Mullen MP, Scaife C, Tosetto M, Nolan B, Wynne K, Hyland J, Sheahan K, Elia G, O'Donoghue D, Fennelly D, O'Sullivan J - BMC Cancer (2014)

Bottom Line: Three proteins (apolipoprotein E (APOE), angiotensinogen (AGT) and vitamin D binding protein (DBP)) were selected for validation studies.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Trinity Centre for Health Sciences, Institute of Molecular Medicine, St, James's Hospital, Dublin 8, Ireland. osullij4@tcd.ie.

ABSTRACT

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.

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Related in: MedlinePlus

Survival and DBP expression. Representative images of DBP expression demonstrating (A) low, (B) medium and (C) high expression, (D) PFS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (E) OS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating a significantly longer OS in patients with low expression, (F) PFS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (G) OS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on OS.
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Fig5: Survival and DBP expression. Representative images of DBP expression demonstrating (A) low, (B) medium and (C) high expression, (D) PFS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (E) OS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating a significantly longer OS in patients with low expression, (F) PFS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (G) OS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on OS.

Mentions: Low expression of stromal DBP demonstrated a significantly longer OS than medium and high expression (Figure 5E), however no differences were seen for PFS (Figure 5D).


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

Martin P, Noonan S, Mullen MP, Scaife C, Tosetto M, Nolan B, Wynne K, Hyland J, Sheahan K, Elia G, O'Donoghue D, Fennelly D, O'Sullivan J - BMC Cancer (2014)

Survival and DBP expression. Representative images of DBP expression demonstrating (A) low, (B) medium and (C) high expression, (D) PFS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (E) OS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating a significantly longer OS in patients with low expression, (F) PFS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (G) OS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on OS.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4289341&req=5

Fig5: Survival and DBP expression. Representative images of DBP expression demonstrating (A) low, (B) medium and (C) high expression, (D) PFS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (E) OS Kaplan meier curve of DBP stromal expression of high, medium and low expression, demonstrating a significantly longer OS in patients with low expression, (F) PFS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on PFS (G) OS Kaplan meier curve of DBP epithelial expression of high, medium and low expression, demonstrating no effect of the three groups on OS.
Mentions: Low expression of stromal DBP demonstrated a significantly longer OS than medium and high expression (Figure 5E), however no differences were seen for PFS (Figure 5D).

Bottom Line: Three proteins (apolipoprotein E (APOE), angiotensinogen (AGT) and vitamin D binding protein (DBP)) were selected for validation studies.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Trinity Centre for Health Sciences, Institute of Molecular Medicine, St, James's Hospital, Dublin 8, Ireland. osullij4@tcd.ie.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus