Circulating Nucleosomes Predict the Response to Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer

Abstract

Purpose:We investigated the potential of circulating, nucleosomal DNA for the early prediction of the efficacy of chemotherapy in patients with advanced lung cancer.Experimental Design: In serum of 212 patients with newly diagnosed non-small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before each new therapeutic cycle. Additionally, carcinoembryonic antigen and cytokeratin 19 fragments (CYFRA 21-1; Elecsys, Roche) were determined before each cycle. The therapeutic success was classified by computed tomography before start of the third cycle according to the World Health Organization criteria.Results: In univariate analysis, responders (patients with remission) showed significantly (P < 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1-8) of nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3 (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to 2 (BV1-2) and from cycle 1 to 3 (BV1-3) compared with nonresponders (patients with stable or progressive disease). Additionally, CYFRA 21-1 (BV1, BV2, BV3, BV1-2, BV1-3) and carcinoembryonic antigen (BV1-2) discriminated significantly between both groups.In multivariate analysis including all parameters available until end of the first therapeutic cycle, nucleosomes (AUC 1-8), CYFRA 21-1 (BV1), stage, and age were independent predictors of therapy response with nucleosomes (AUC 1-8) having the strongest impact. Conclusion:Circulating nucleosomes in combination with oncological biomarkers are valuable for the early estimation of the efficacy of chemotherapy in patients with lung cancer.

Circulating Mitochondrial Nucleic Acids Have Prognostic Value for Survival in Patients with Advanced Prostate Cancer

“…Other groups have since reported an association of high plasma DNA levels with poor prognosis or a lack of response to treatment (6,9). mtDNA encodes for proteins of the respiratory chain and cells can contain hundreds to thousands of mtDNA copies per cell instead of two copies of genomic DNA.…”

Research Progress in Applying Proteomics Technology to Explore Early Diagnosis Biomarkers of Breast Cancer, Lung Cancer and Ovarian Cancer

“…Washam et al (2011) (Kulpa, et al, 1999;Molina, et al, 2003;Molina, et al, 2005;Holdenrieder, et al, 2004;Ardizzoni, et al, 2006) Barak, et al, 2004) (Hatzakis, et al, 2002;Muley, et al, 2002;Barlési, et al, 2004) Kashiwabara , et al, 2000;Pujol, et al, 2001;Hatzakis, et al, 2002;Reinmuth, et al, 2002;Kulpa, et al, 2002;Merle, et al, 2003;Vollmer, et al, 2003;Pujol, et al, 2003;Pujol, et al, 2004;Barlesi, et al, 2005 (Bonner, et al, 2000;Shibayama, et al, 2001;Satoh, et al, 2002;Massacesi, et al, 2002;Molina, et al, 2003;Muley, et al, 2004;Molina, et al, 2004;Schneider, et al, 2006) …”

Biomarkers for the lung cancer diagnosis and their advances in proteomics

“…CEA alone has limit to diagnosis and is preferably used in combination with CYFRA. As a therapy response monitoring indicator, CEA is used for advanced NSCLC and adenocarcinoma (49,50). However, CEA and CYFRA have been also found to be associated with other types of cancers such as colorectal cancers (51,52).…”