NYU Lung Cancer Biomarker Center

描述（由申请人提供）：纽约大学肺癌生物标志物中心CVC招募了1143名高危吸烟者（SCREENING COHORT）用于肺癌的早期检测。我们与Harvey Pass，MD和胸外科合作，在R/0肺癌COHORT中评估了1047例研究受试者。采集标本、血液（100 ml）、肺量测定、痰液和CT扫描。52%的筛选队列有非钙化结节（NCN），获得3771次CT扫描以评估生长率。胸部肿瘤22例，肺腺癌18例。Sidransky Johns霍普金斯的生物标记合作）在肺癌患者的血浆中鉴定了一组具有启动子高甲基化的基因。与这一发现相一致，我们注意到与NCN高危吸烟者相比，肺癌患者血浆S-腺苷甲硫氨酸（甲基化途径中的关键中间体）增加。利用预留的资金，我们在PBMC中显示了29个基因的表达模式，将肺癌与高风险对照区分开来，L，Showe（Wistar，UPenn），M-s Tang及其同事证明了DNA加合物发生在p53和K-ras的热点突变位点，修复不良导致加合物持续存在。使用GC/MS中测量的烷烃的组合，呼出气预测具有高AUC的肺癌。我们的研究计划是用300名新的高危吸烟者、1000名随访的NCN和> 250名肺癌来扩大我们的CVC。我们将通过CT扫描评估NCN，以便早期发现。我们将通过测量血液丙烯醛DNA加合物和PBMC DNA修复能力来确定高危吸烟者患肺癌的风险。我们将开展一项针对200例肺癌病例和200例匹配对照的3期验证病例对照研究，以及一项针对600例肺癌发病率>40例的高危吸烟者的4期验证队列研究。我们将评估血清中的肿瘤相关抗原、自身抗体、PBMC中的基因表达模式和microRNA的通路控制。重要的是，我们将在相同的前瞻性高风险吸烟者队列中交叉验证生物标志物组。

DESCRIPTION (provided by applicant): The NYU Lung Cancer Biomarker Center CVC has recruited 1143 high-risk smokers (SCREENING COHORT) for the early detection of lung cancer. We have evaluated 1047 study subjects in our R/0 LUNG CANCER COHORT in collaboration with Harvey Pass, MD and the Division of Thoracic Surgery. Questionnaires, blood (100ml), spirometry, sputum, and CT-scans are obtained. 52% of the SCREENING COHORT had non-calcified nodules (NCN) with 3771 CT-Scans obtained to assess growth rates. 22 thoracic neoplasms were diagnosed with 18 lung adenocarcinomas. Biomarker collaborations with D, Sidransky Johns Hopkins) identified a panel of genes with promoter hypermethylations in plasma from lung cancer patients. Consistent with this finding, we noted increased plasma S- adenosylmethionine, a key intermediate in the methylation pathway, in lung cancer patients compared to high-risk smokers with NCN. Using set aside funds, we showed a 29-gene expression pattern in PBMC that separated lung cancer from high-risk controls with L, Showe (Wistar, UPenn), M-s Tang and colleagues demonstrated DNA adducts occurred at hot spot mutation sites in p53 and K-ras, and that poor repair contributed to adduct persistence. Exhaled breath predicted lung cancer with high AUC using combinations of alkanes measured in GC/MS. Our research plan is to expand our CVC with 300 new high-risk smokers, 1000 follow-up NCNs, and > 250 lung cancers. We will evaluate NCN by CT- scans for early detection. We will determine risk for lung cancer among high-risk smokers by measuring blood acrolein DNA adducts and PBMC DNA repair capacity. We will develop a phase 3 validation case control study of 200 lung cancer cases and 200 matched controls and a phase 4 validation cohorts study of 600 high-risk smokers with >40 incident lung cancers. We will evaluate serum for tumor-associated antigens, auto-antibodies, gene expression patterns in PBMC and pathway control by microRNAs. Importantly, we will cross validate biomarker panels in the same prospective high risk smoker cohorts.