Serum level of soluble 70-kD heat shock protein is associated with high mortality in patients with colorectal cancer without distant metastasis

Abstract

Many findings indicate that measuring the serum concentration of soluble 70-kD heat shock protein (soluble HSP70) may provide important information in cardiovascular, inflammatory, and pregnancy-related diseases; however, only scarce data are available in cancer. Therefore, using a commercial ELISA kit, we measured soluble HSP70 concentration in the sera of 179 patients with colorectal cancer. We investigated the relationship between soluble HSP70 concentration and mortality, during 33.0 (24.4- 44.0)months long follow-up. High (>1.65 pg/ml, median concentration) soluble HSP70 level was a significant (hazard ratio: 1.88 (1.20-2.96, p=0.005) predictor of mortality during the follow-up period. When we compared the soluble HSP70 levels in patients with non-resected primary tumors as compared to those who were recruited into the study 4-6 weeks after the tumor resection they were found to be significantly (p=0.020) higher in the former group. Since the patients with non-resected primary tumors had also distant metastasis and died early, we limited the further analysis to 142 patients with no distant metastasis at the beginning of the follow-up. This association remained significant even after multiple Cox-regression analysis had been performed to adjust the data for age and sex (p=0.028); age, sex, and TNM-T stage (p=0.041); age, sex, and TNM-N stage (p=0.021); age, sex, and histological grade (p=0.023); or age, sex, and tumor localization (p=0.029). Further analysis showed that the significant association between high HSP70 levels and poor survival is in the strongest in the group of <70-year-old female patients (HR: 5.52 (2.02-15.15), p=0.00l), as well as in those who were in a less advanced stage of the disease at baseline. These novel findings indicate that the serum level of soluble HSP70 might prove a useful, stage-independent prognostic marker in colorectal cancer without distant metastasis.