NYU Lung Cancer Biomarker Center

纽约大学肺癌生物标志物中心

• 批准号: 8698331
• 负责人: WILLIAM N ROM
• 金额: $ 63.01万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-08 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698331
• 关键词: Acrolein; Alkanes; Antibodies; Biological Markers; Blood; Cancer Patient; Case-Control Studies; Cohort Studies; Collaborations; DNA Adducts; DNA Repair; Diagnosis; Early Diagnosis; Exhalation; Funding; Gene Expression Profile; Genes; Growth; Hot Spot; Hypermethylation; KRAS2 gene; Lung Adenocarcinoma; Malignant neoplasm of lung; Measures; Methylation; MicroRNAs; Mutation; Nodule; Pathway interactions; Peripheral Blood Mononuclear Cell; Phase; Plasma; Questionnaires; Recruitment Activity; Research; Risk; S-Adenosylmethionine; Serum; Site; Smoker; Spirometry; Sputum; Study Subject; Thoracic Neoplasms; Thoracic Surgical Procedures; Tumor Antigens; Validation; X-Ray Computed Tomography; adduct; cohort; follow-up; high risk; lung cancer screening; promoter; prospective; repaired; screening

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.

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（筛查队列），用于肺癌的早期检测。我们与医学博士 Harvey Pass 和胸外科合作评估了 R/0 肺癌队列中的 1047 名研究对象。获取问卷、血液（100ml）、肺活量测定、痰液和CT扫描。通过 3771 次 CT 扫描来评估生长率，筛查队列中 52% 的人患有非钙化结节 (NCN)。诊断出胸部肿瘤 22 例，其中肺腺癌 18 例。 Biomarker 与约翰·霍普金斯大学 (D, Sidransky Johns Hopkins) 合作鉴定了肺癌患者血浆中启动子高甲基化的一组基因。与这一发现一致的是，我们注意到，与 NCN 的高危吸烟者相比，肺癌患者的血浆 S-腺苷甲硫氨酸（甲基化途径中的关键中间体）有所增加。利用预留资金，我们展示了 PBMC 中的 29 个基因表达模式，该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 DNA 加合物发生在 p53 和 p53 的热点突变位点K-ras，而不良的修复导致了加合物的持久存在。使用 GC/MS 中测量的烷烃组合，呼出气以高 AUC 预测肺癌。我们的研究计划是通过 300 名新的高危吸烟者、1000 名后续 NCN 和 > 250 种肺癌来扩大我们的 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 名匹配对照的 3 期验证病例对照研究，以及一项针对 600 名患有超过 40 例肺癌的高危吸烟者的 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 中的基因表达模式以及 microRNA 的通路控制。重要的是，我们将在相同的预期高风险吸烟者群体中交叉验证生物标志物组。

项目成果

Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs.

• DOI: 10.1513/annalsats.201310-339fr
• 发表时间: 2014-01-01
• 期刊: Annals of the American Thoracic Society
• 影响因子: 8.3
• 作者: Segal, Leopoldo N;Rom, William N;Weiden, Michael D
• 通讯作者: Weiden, Michael D

Integrated Metabolomics and Proteomics Highlight Altered Nicotinamide- and Polyamine Pathways in Lung Adenocarcinoma.

• DOI: 10.1093/carcin/bgw205
• 发表时间: 2017-03
• 期刊: Carcinogenesis
• 影响因子: 4.7
• 作者: Fahrmann JF;Grapov DD;Wanichthanarak K;DeFelice BC;Salemi MR;Rom WN;Gandara DR;Phinney BS;Fiehn O;Pass H;Miyamoto S
• 通讯作者: Miyamoto S

Prediction of lung cancer using volatile biomarkers in breath.

使用呼吸中的挥发性生物标志物预测肺癌。

• DOI: 10.3233/cbm-2007-3204
• 发表时间: 2007
• 期刊: Cancer biomarkers : section A of Disease markers
• 作者: Phillips,Michael;Altorki,Nasser;Austin,JohnHM;Cameron,RobertB;Cataneo,ReneeN;Greenberg,Joel;Kloss,Robert;Maxfield,RogerA;Munawar,MuhammadI;Pass,HarveyI;Rashid,Asif;Rom,WilliamN;Schmitt,Peter
• 通讯作者: Schmitt,Peter

Experimental human exposure to air pollutants is essential to understand adverse health effects.

• DOI: 10.1165/rcmb.2013-0253ps
• 发表时间: 2013-11
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: W. Rom;H. Boushey;A. Caplan

Resection of non-small cell lung cancers reverses tumor-induced gene expression changes in the peripheral immune system.

• DOI: 10.1158/1078-0432.ccr-11-0737
• 发表时间: 2011-09-15
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Kossenkov AV;Vachani A;Chang C;Nichols C;Billouin S;Horng W;Rom WN;Albelda SM;Showe MK;Showe LC
• 通讯作者: Showe LC