Circulating Nucleosomes and Cytokeratin 19-Fragments in Patients with Colorectal Cancer During Chemotherapy

Abstract

Background: Intracellular components, such as nucleosomal DNA and cytokeratins, are released from cells during apoptosis, which occurs spontaneously in elevated amounts in patients with various tumors, as well as during treatment with chemotherapeutic drugs. Patients and Methods: Sera of 30 patients with colorectal cancer, stage Dukes' B to D, who received adjuvant (N=15) or palliative (N=15) chemotherapy, were investigated. The response to therapy was objectified by imaging techniques after 3 cycles of therapy. Circulating nucleosomes and cytokeratin 19-fragments (CYFRA 21-1; both by Elecsys, Roche) were determined before (day 1) and after (day 3) each cycle of chemotherapy. Results: Nucleosomal DNA typically increased during the chemotherapeutic cycles - most notably in the first 2 cycles (median: INC1: 22% and INC2: 49%) - being applied as adjuvant or palliative therapy. Whereas patients with adjuvant therapy mainly had declining baseline values (median: BV1-2: -21%, BV1-3: -36%), those with palliative treatment showed equal or increasing values (median: BV1-2: 30%, BV1-3: 0%). Within the group of patients with palliative treatment, those with progression of disease (N=6) had increasing baseline values (BV1-3: 33%) and high increases during the cycles (median: INC1: 232% and INC2: 60%; those with no progression showed decreasing baseline values (BV1-3: -22%) and mainly decreases during the cycles (median: INC1: -38% and INC2: -52%). CYFRA 21-1 showed less change during chemotherapeutic cycles (adjuvant: INC1: 17%, INC2: 22%; palliative: INC1: 9%, INC2: 11%) and concerning the baseline values (adjuvant: BV1-2: 1%, BV1-3: -6%; palliative: BV1-2: -3%, BV1-3: 9%). The absolute levels of pretherapeutic values were higher for those with progression (median: 2.1 ng/mL) than for those without progression (1.3 ng/mL). Conclusion: The kinetics of circulating nucleosomes in patients with colorectal cancer show characteristic differences between adjuvant and palliative chemotherapy as well as concerning the response to palliative chemotherapy.