title: Circulating nucleosomes and immunogenic cell death markers HMGB1, sRAGE and DNAse in patients with advanced pancreatic cancer undergoing chemotherapy.
abstract: Serum biomarkers are urgently needed for patient stratification and efficient treatment monitoring in pancreatic cancer (PC). Within a prospective diagnostic observation study, blood samples were obtained from 78 patients with advanced PC before and weekly during the course of palliative chemotherapy. Circulating nucleosomes and immunogenic cell death markers, high-mobility group box 1 (HMGB1), soluble receptors of advanced glycation end products (sRAGE) and DNAse activity, were measured by enzyme-linked immunosorbent assay and correlated with results of radiological staging after 2 months of treatment, with time to progression (TTP) and overall survival (OS). Median TTP and OS of PC patients were 3.9 and 7.7 months, respectively. Pretherapeutic baseline biomarker levels did not correlate with objective response; however, nucleosome levels on day (d) 28 were higher (p = 0.048) and sRAGE levels at time of staging (d56) were lower in progressive patients (p = 0.046). Concerning estimation of prognosis, high nucleosome levels (d7, d14, d21 and d56), low sRAGE levels (d56) and DNAse activity courses (d0-d7) correlated with TTP, whereas high nucleosomes (d7, d14 and d56), high HMGB1 (d21 and d56) and DNAse (d0-d7) were associated with OS. After adjustment to Karnofsky performance score, nucleosomes and HMGB1 (both d56) and DNAse (d0-d7) remained independent prognostic factors. Thus, courses of circulating nucleosomes and immunogenic cell death markers HMGB1 and sRAGE show prognostic relevance in PC patients undergoing chemotherapy.
authors.affiliation: Institute of Clinical Chemistry, University Hospital Munich-Grosshadern, Munich, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Wittwer
authors.forename: Stefan
authors.initials: S
authors.lastname: Boeck
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D003851:Deoxyribonucleases / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; D009707:Nucleosomes; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003851:Deoxyribonucleases
keywords: DNAse activity; HMBG1; nucleosomes; pancreatic cancer; prognosis; sRAGE