Aberrant cystatin-C expression in blood from patients with breast cancer is a suitable marker for monitoring tumor burden

The present study was performed to evaluate the efficacy of circulating cystatin-C as a tumor monitoring biomarker at different clinical time points in patients with breast cancer over a long-term follow-up period. In addition, the secretory rate of circulating cystatin-C from cancer tissue was investigated by comparing the blood and tissue expression levels of cystatin-C. Blood samples from healthy volunteers (40 males and 40 females) were obtained at yearly health examinations if laboratory and imaging abnormalities were not detected. Blood samples from 34 patients with breast cancer were obtained at 205 different time points of clinical progression. Blood levels of cystatin-C were measured using ELISA and the tissue levels were measured using immunohistochemistry. No age-associated effect was observed in male and female blood cystatin-C levels. The positivity rate was 46% in patients (38/83) and 40% in samples collected at different time points (82/205). Blood cystatin-C levels were lowest following surgery compared with patients with systemic metastasis (P<0.001). The sensitivity, specificity and accuracy rates of ELISA were 53.6, 63.6 and 53.9%, respectively. The concordance rate between blood and tissue expression was 38%. The main reason for discordance between tissue and serum expression of cytostatin-C came from low serum positivity in samples showing tissue cytostatin-C (3/11, 27%). The specificity between cytostatin-C and CA-125 was highest in tumor absence state. In conclusion, elevated blood levels of cystatin-C were observed in 40% of breast cancer cases and were tumor-volume dependent. However, the concordance rate between tissue and blood was quite low, suggesting tumor heterogeneity of cystatin-C expression or co-acting pathway activation, such as cathepsin D. As one-third of breast cancer tissues express cystatin-C without cancer antigen 15-3 elevation, cystatin-C may represent a good tumor-monitoring marker in breast cancer.