PNAS：新研究表明利用简单的血液测试有望诊断肺癌

jitianxing7021

http://www.ncbi.nlm.nih.gov/pubmed/23074256/ y5 v* f3 h  g
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Variant Ciz1 is a circulating biomarker for early-stage lung cancer: K- j/ {! C* P4 O- J

: C8 w& T. n, h. N; I# W- YGillian Higginsa,b, Katherine M. Ropera,b, Irene J. Watsona,b, Fiona H. Blackhallc, William N. Romd, Harvey I. Passe, Justin F. X. Ainscoughf, and Dawn Coverley) Y* p4 U% T! D- v
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There is an unmet need for circulating biomarkers that can detect early-stage lung cancer. Here we show that a variant form of the nuclear matrix-associated DNA replication factor Ciz1 is present in 34/35 lung tumors but not in adjacent tissue, giving rise to stable protein quantifiable by Western blot in less than a microliter of plasma from lung cancer patients. In two independent sets, with 170 and 160 samples, respectively, variant Ciz1 correctly identified patients who had stage 1 lung cancer with clinically useful accuracy. For set 1, mean variant Ciz1 level in individuals without diagnosed tumors established a threshold that correctly classified 98% of small cell lung cancers (SCLC) and non-SCLC patients [receiver operator characteristic area under the curve (AUC) 0.958]. Within set 2, comparison of patients with stage 1 non-SCLC with asymptomatic age-matched smokers or individuals with benign lung nodules correctly classified 95% of patients (AUCs 0.913 and 0.905), with overall specificity of 76% and 71%, respectively. Moreover, using the mean of controls in set 1, we achieved 95% sensitivity among patients with stage 1 non-SCLC patients in set 2 with 74% specificity, demonstrating the robustness of the classification. RNAi-mediated selective depletion of variant Ciz1 is sufficient to restrain the growth of tumor cells that express it, identifying variant Ciz1 as a functionally relevant driver of cell proliferation in vitro and in vivo. The data show that variant Ciz1 is a strong candidate for a cancer-specific single marker capable of identifying early-stage lung cancer within at-risk groups without resort to invasive procedures4 g" K- }! t: y- r) ?