title: Screening for circulating nucleic acids and caspase activity in the peripheral blood as potential diagnostic tools in lung cancer.
abstract: The focus of the current investigational study was to examine whether circulating nucleic acids (i.e., DNA and microRNAs) have the potential to become suitable blood-based markers for diagnosis and progression of lung cancer. The concentrations of cell-free DNA and four circulating microRNAs (miR10b, miR34a, miR141 and miR155) as well as the caspase activity were measured in serum of 35 lung cancer patients (19 non-small-cell lung cancer, 8 small cell lung cancer patients and 8 patients with indefinite cancer type), 7 patients with benign lung tumors and 28 healthy individuals by PicoGreen, TaqMan MicroRNA, and Caspase-Glo®3/7 assay, respectively. The data were correlated with the established risk factors for lung cancer progression. The concentrations of cell-free DNA (p = 0.0001), serum microRNAs (p = 0.0001) and caspase activities (p = 0.0001) significantly discriminated cancer patients from healthy individuals. Serum DNA, caspase activities and RNA levels could not distinguish between patients with benign lung disease and cancer patients. However, the levels of miR10b (p = 0.002), miR141 (p = 0.0001) and miR155 (p = 0.007) were significantly higher in lung cancer patients than those in patients with benign disease. As determined by the Spearman-Rho test, high levels of cell-free DNA significantly correlated with elevated circulating caspase activities (p = 0.0001). In lung cancer patients high serum miR10b values associated with lymph node metastasis (p < 0.03) and elevated levels of TPA (tissue polypeptide antigen, p = 0.01), whereas high serum miR141 values associated with elevated levels of uPA (urokinase plasminogen activator, p = 0.02). The findings of our pilot study suggest that the assays for circulating DNA, microRNAs and caspase activities in blood might become novel minimally invasive diagnostic tools for detection and risk assessment of lung cancer, provided that their clinical utility can be confirmed in larger prospective trials.
authors.affiliation: Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Roth
authors.forename: Sabine
authors.initials: S
authors.lastname: Kasimir-Bauer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
mesh_terms: D000328:Adult; D000368:Aged; D020169:Caspases / Q000097:blood*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000097:blood*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D008403:Mass Screening; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009696:Nucleic Acids / Q000097:blood*
chemical_list: D004273:DNA, Neoplasm; D035683:MicroRNAs; D009696:Nucleic Acids; D020169:Caspases