Bisgin et al. BMC Cancer 2012, 12:58 http://www.biomedcentral.com/1471-2407/12/58 Page 3 of 5 Figure 1 Serum sTRAIL levels. No difference between two groups (P = 0.50) before bevacizumab treatment: 1.12 ± 0.04 ng/ml in metastatic colon cancer patients and 1.17 ± 0.08 ng/ml in healthy control individuals. Discussion and conclusions MCRC is mainly treated with combination of bevacizu- mab and irinotecan or oxaliplatin-based chemotherapy. The role of TRAIL and another apoptotic marker FAS/ FASL systems in CRC patients treated with chemothera- peutic agents has been discussed previously [31-33]. The use of sTRAIL is a novel concept for which few data exist. We evaluated sTRAIL ratio as a marker of che- motherapeutic responsiveness in MCRC patients. This is believed to be the first study in which changes in levels of sTRAIL after bevacizumab treatment have been esti- mated in overall survival of MCRC patients. In this study, we compare the levels of sTRAIL in responders versus non-responders to bevacizumab ther- apy. In responding patients, sTRAIL level increased, but Figure 2 Serum sTRAIL levels after treatment. Elevated levels of sTRAIL were found in seven out of 16 metastatic colon cancer patients whose serum sTRAIL concentrations were similar to those of healthy age- and sex-matched control individuals (n = 10) before bevacizumab therapy, as seen in Figure 1. These increases were significant compared with pretreatment measurements (P < 0.001). The increase or decrease in the serum levels were shown as percentage change in serum sTRAIL. Table 2 Change in serum sTRAIL levels and association with survival. Response Status Alive (n = 7) Dead (n = 9) Statistical analysis (unpaired t-test) Survival (month) 20,6 ± 0,5 9,4 ± 0,9 p < 0,05 (p = 0,0001) Serum sTRAIL Level (ng/ ml) 1,38 ± 0,10 0,92 ± 0,05 p < 0,05 (p = 0,0002) Metastatic colon cancer patients who were treated with bevacizumab, and had increased levels of serum sTRAIL after treatment, had an extended median survival time up to 20.6 months. In contrast, median survival was 9.4 months for patients with decreased or unchanged sTRAIL after the bevacizumab therapy the level decreased or was unchanged in non-respon- ders. This significant change may be a result of the effect of bevacizumab on cancer cells via apoptosis. Another study has found that, although there was no significant difference between sTRAIL, soluble death receptor (sDR)4 and sDR5 levels in MCRC patients before and after treatment, significant correlations were observed between post-treatment sFASL and sDR4, post-treatment sFAS and sTRAIL, post-treatment sTRAIL and sFAS/sFASL ratio, and post-treatment sFASL and sDR5 [34]. This controversy may also have been due to the patients enrolled in the study. Although we chose newly diagnosed patients who had bevacizu- mab as first-line treatment, in the other study, patients were mostly treated with bevacizumab-based che- motherapy in the second-line setting after failure of oxa- liplatin-based chemotherapy. There have been many studies that have focused on identifying biomarkers for prediction of bevacizumab efficacy. The most obvious protein biomarker to select for testing bevacizumab efficacy is VEGF, but no studies have yet found changes in VEGF concentrations during therapy to have consistent predictive value [35]. One study has found that circulating levels of intercellular adhesion molecule (ICAM)-1 to be at least potentially predictive of survival benefit. Other studies have sug- gested that neutropenia might have a negative effect on bevacizumab efficacy. There have also been other stu- dies that have concluded that polymorphisms in the VEGF pathway may have predictive value [36,37]. How- ever, although several candidate biomarkers have already been described, including tumor and plasma VEGF, cir- culating E-selectin, ICAM-1 and vascular cell adhesion molecule-1, much more work is needed to determine the most effective biomarkers and thus to select the patients that are most likely to benefit from bevacizu- mab therapy [36]. As a conclusion, our study gave a different perspec- tive on MCRC and bevacizumab treatment efficacy in relation to apoptosis and serum sTRAIL levels. The