RESUMEN
Colorectal cancer (CRC) is the third most common cancer worldwide. Successful treatment is heavily dependent on tumor stage at the time of detection, but unfortunately CRC is often only detected in advanced stages. New biomarkers in the form of genes or proteins that can be used for diagnosis, prognostication, follow-up, and treatment selection and monitoring could be of great benefit for the management of CRC. Furthermore, proteins could prove valuable new targets for therapy. Therefore, clinical proteomics has gained a lot of scientific interest in this regard. To get an overall insight into the extent to which this research has contributed to a better management of CRC, we give a comprehensive overview of the results of proteomics research on CRC, focusing on expression proteomics, in other words, protein profiling studies. Furthermore, we evaluate the potential of the discriminating proteins identified in this research for clinical use as biomarkers for (early) diagnosis, prognosis and follow-up of CRC or as targets for new therapeutic regimens.
RESUMEN
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.
RESUMEN
BACKGROUND: Light-induced fluorescence endoscopy (LIFE) may improve the detection of high-grade dysplasia (HGD) and early stage cancer (EC) in Barrett's esophagus (BE). The aim of this study was to compare LIFE with standard endoscopy (SE) in a randomized crossover study. METHODS: Fifty patients with BE underwent SE and LIFE in a randomized sequence (4 to 6-week interval between procedures). The two procedures were performed by two different endoscopists who were blinded to the findings of the other examination. Targeted biopsy specimens were taken from detected lesions, followed by random biopsy specimens with a 2-cm interval, 4-quadrant protocol. Biopsy specimens were routinely evaluated and subsequently reviewed by a single, blinded expert GI pathologist. RESULTS: Targeted biopsy specimens had a sensitivity for the diagnosis of HGD/EC of 62% (8/13) for both techniques. The overall sensitivity (all biopsy specimens) was 85% for SE and 69% for LIFE (p = 0.69). All targeted biopsy specimens had a positive predictive value (PPV) for HGD/EC of 41% for SE and 28% for LIFE (p = 0.40); autofluorescence-targeted biopsy specimens had a PPV of 13%. False-positive lesions had a significantly higher rate of acute inflammation than random biopsy specimens. CONCLUSIONS: In this study, LIFE did not improve the detection of HGD or EC in patients with BE compared with SE.