Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients

Radioembolization therapy (RE) is an efficient locoregional treatment for liver metastases from colorectal cancer. Serum biomarkers involved in immunogenic cell death are potentially valuable for early predicting therapy response and estimating prognosis. In a prospective observation study, blood samples were taken from 49 consecutive colorectal cancer patients with extensive hepatic metastases before, 24 and 48 hr after RE. Serum levels of high mobility group box 1 (HMGB1), receptor of glycation end products (RAGE) and activity of desoxyribonuclease were compared with response to therapy regularly determined radiologically 3 months after therapy and with overall survival. Serum levels of HMGB1 were increased already 24 hr after RE, while RAGE levels were decreased and DNAse remained unchanged. In radiological staging, 35 patients demonstrated disease progression while 14 patients had stable disease or remission. Serum HMGB1 levels 24 hr after RE were significantly higher in progressive than in nonprogressive patients while for RAGE and DNAse no difference was observed between the response groups. Concerning overall survival, high pretherapeutic (0 hr) and 24 hr levels of HMGB1 were associated with poor outcome. Multivariate analysis including HMGB1, tumor, liver and inflammation markers revealed HMGB1 and CRP as independent prognostic parameters. HMGB1 is a valuable serum biomarker for early estimation of therapy response and prognosis in colorectal cancer patients with liver metastases undergoing RE therapy. What's new? Radioembolization therapy (RE) is an effective therapy for colorectal cancer patients with liver metastases. However, data on predictive factors to assess treatment response are lacking. The authors examined the role of HMGB1, a nuclear protein released during cell death and acting as a danger-associated molecular pattern (DAMP) protein recognized by specific immune cells. Serum levels of HMGB1 were found to rise early after RE therapy, and high pre- and posttherapeutic levels of serum HMGB1 were associated with poor treatment response with unfavorable prognosis in uni- and multivariate analyses. These results point to HMGB1 as a potential new biomarker for treatment response in RE therapy.