Detection of Colorectal Cancer by Serum and Tissue Protein Profiling: A Prospective Study in a Population at Risk

Abstract

Colorectal cancer (CRC) is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation—time of flight mass spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP). Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52) and CRC (n = 47) were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM). We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups.

Search for Breast Cancer Biomarkers in Fractionated Serum Samples by Protein Profiling With SELDI‐TOF MS

“…Additionally, differences may be due to differences in type of sample that was investigated; tissue vs. serum. Such a difference was also found by Engwegen et al ; a specific protein was lower in serum samples of colorectal cancer patients than in controls, while the same protein was higher in colorectal cancer tissue compared with healthy colon tissue of the same subjects (hyperplastic polyps) .…”

A novel method for screening colorectal cancer by infrared spectroscopy of peripheral blood mononuclear cells and plasma

“…This finding indicates no major difference in the immune activity or plasma biochemical composition between small and large polyps. Other studies present possible correlations between plasma proteins and polyp size [34,35]. Although there is evidence for correlation between immune activity and stage of colorectal cancer [10], to our knowledge, there is no similar evidence reported in the case of polyp size.…”

Comparative Serum Proteomic Analysis of Serum Diagnosis Proteins of Colorectal Cancer Based on Magnetic Bead Separation and MALDI-TOF Mass Spectrometry

“…Wang et al identified two serum protein biomarkers (3961 and 5200 m/z) useful for monitoring colorectal cancer (Wang et al, 2009). Another recent study confirmed the decreased serum levels of apolipoprotein C-1 in CRC (Engwegen et al, 2008). Additionally, protein markers associated with lymph node metastases in colorectal and prostate cancer have been profiled (Pang et al, 2010;Fan et al, 2011).…”