NYU Lung Cancer Biomarker Center

Summary

Principal Investigator: William N Rom
Abstract: 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.
Funding Period: 2000-05-08 - 2015-12-31
more information: NIH RePORT

Top Publications

  1. ncbi Prediction of lung cancer using volatile biomarkers in breath
    Michael Phillips
    Menssana Research Inc, Fort Lee, NJ 07024 6510, USA
    Cancer Biomark 3:95-109. 2007
  2. pmc Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer
    Rachel M Ostroff
    SomaLogic, Boulder, Colorado, United States of America
    PLoS ONE 5:e15003. 2010
  3. pmc Resection of non-small cell lung cancers reverses tumor-induced gene expression changes in the peripheral immune system
    Andrew V Kossenkov
    The Wistar Institute, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 17:5867-77. 2011
  4. pmc Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry
    Jane P Ko
    Department of Radiology, New York University Langone Medical Center, 560 1st Ave, New York, NY 10016, USA
    Radiology 262:662-71. 2012
  5. pmc Longitudinal multistage model for lung cancer incidence, mortality, and CT detected indolent and aggressive cancers
    William D Hazelton
    Fred Hutchinson Cancer Research Center, Public Health Sciences Division, 1100 Fairview Avenue North, Box 19024, Seattle, WA 98109, USA
    Math Biosci 240:20-34. 2012
  6. pmc CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohort
    Alissa K Greenberg
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, USA
    PLoS ONE 7:e39403. 2012
  7. pmc Effect of CpG methylation at different sequence context on acrolein- and BPDE-DNA binding and mutagenesis
    Hsiang Tsui Wang
    Department of Environmental Medicine, Pathology and Medicine, New York University School of Medicine, Tuxedo Park, New York 10987, USA
    Carcinogenesis 34:220-7. 2013
  8. pmc Variant Ciz1 is a circulating biomarker for early-stage lung cancer
    Gillian Higgins
    Cizzle Biotech, University of York, Yorkshire YO10 5DD, United Kingdom
    Proc Natl Acad Sci U S A 109:E3128-35. 2012
  9. pmc Aryl hydrocarbon receptor and lung cancer
    Junchieh J Tsay
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, NY, USA
    Anticancer Res 33:1247-56. 2013
  10. pmc Plasma osteopontin velocity differentiates lung cancers from controls in a CT screening population
    Sasha Joseph
    Thoracic Oncology Laboratory, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, NY 10016, USA
    Cancer Biomark 12:177-84. 2012

Detail Information

Publications24

  1. ncbi Prediction of lung cancer using volatile biomarkers in breath
    Michael Phillips
    Menssana Research Inc, Fort Lee, NJ 07024 6510, USA
    Cancer Biomark 3:95-109. 2007
    ..g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer...
  2. pmc Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer
    Rachel M Ostroff
    SomaLogic, Boulder, Colorado, United States of America
    PLoS ONE 5:e15003. 2010
    ..Here we present a comprehensive clinical biomarker study of lung cancer and the first large-scale clinical application of a new aptamer-based proteomic technology to discover blood protein biomarkers in disease...
  3. pmc Resection of non-small cell lung cancers reverses tumor-induced gene expression changes in the peripheral immune system
    Andrew V Kossenkov
    The Wistar Institute, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 17:5867-77. 2011
    ....
  4. pmc Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry
    Jane P Ko
    Department of Radiology, New York University Langone Medical Center, 560 1st Ave, New York, NY 10016, USA
    Radiology 262:662-71. 2012
    ..To determine the precision of a three-dimensional (3D) method for measuring the growth rate of solid and subsolid nodules and its ability to detect abnormal growth rates...
  5. pmc Longitudinal multistage model for lung cancer incidence, mortality, and CT detected indolent and aggressive cancers
    William D Hazelton
    Fred Hutchinson Cancer Research Center, Public Health Sciences Division, 1100 Fairview Avenue North, Box 19024, Seattle, WA 98109, USA
    Math Biosci 240:20-34. 2012
    ..Females may have an inherently higher proportion of indolent lung cancers than males, or aggressive lung cancers may be brought into check by the immune system more frequently among females than males...
  6. pmc CT scan screening for lung cancer: risk factors for nodules and malignancy in a high-risk urban cohort
    Alissa K Greenberg
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, New York, USA
    PLoS ONE 7:e39403. 2012
    ..We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant...
  7. pmc Effect of CpG methylation at different sequence context on acrolein- and BPDE-DNA binding and mutagenesis
    Hsiang Tsui Wang
    Department of Environmental Medicine, Pathology and Medicine, New York University School of Medicine, Tuxedo Park, New York 10987, USA
    Carcinogenesis 34:220-7. 2013
    ..These results indicate that both CpG sequence context and the chemical nature of the carcinogens are crucial factors for determining the effect of CpG methylation on mutagenesis...
  8. pmc Variant Ciz1 is a circulating biomarker for early-stage lung cancer
    Gillian Higgins
    Cizzle Biotech, University of York, Yorkshire YO10 5DD, United Kingdom
    Proc Natl Acad Sci U S A 109:E3128-35. 2012
    ..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 procedures...
  9. pmc Aryl hydrocarbon receptor and lung cancer
    Junchieh J Tsay
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University School of Medicine, New York, NY, USA
    Anticancer Res 33:1247-56. 2013
    ..In this review article we summarize the current understanding of AhR and its role in the development of lung cancer, including its influence on cell proliferation, angiogenesis, inflammation, and apoptosis...
  10. pmc Plasma osteopontin velocity differentiates lung cancers from controls in a CT screening population
    Sasha Joseph
    Thoracic Oncology Laboratory, Department of Cardiothoracic Surgery, NYU School of Medicine, New York, NY 10016, USA
    Cancer Biomark 12:177-84. 2012
    ..We hypothesize that changes in plasma OPN over time (i.e., OPN velocity [OPNV]) can differentiate NSCLC patients from those without cancer in a CT screening population...
  11. ncbi Experimental human exposure to air pollutants is essential to understand adverse health effects
    William N Rom
    1 Division of Pulmonary, Critical Care, and Sleep Medicine, and
    Am J Respir Cell Mol Biol 49:691-6. 2013
    ..We find that these studies appear to have been done with proper approval of institutional review boards, were done with informed consent from the participants, and have rarely been associated with serious adverse events...
  12. pmc Optical detection of buccal epithelial nanoarchitectural alterations in patients harboring lung cancer: implications for screening
    Hemant K Roy
    Department of Medicine, NorthShore University HealthSystem Biomedical Engineering Department, Northwestern University, Evanston, Illinois, USA
    Cancer Res 70:7748-54. 2010
    ..Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs...
  13. pmc S-adenosylmethionine as a biomarker for the early detection of lung cancer
    Alissa K Greenberg
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    Chest 132:1247-52. 2007
    ..We hypothesized that AdoMet levels were elevated in patients with lung cancer and may prove useful as a biomarker for early lung cancer...
  14. ncbi In vitro mechanisms of lovastatin on lung cancer cell lines as a potential chemopreventive agent
    Elena Maksimova
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Lung 186:45-54. 2008
    ..g., reversing ground glass opacities detected on CT scans or resolving airway preneoplasias detected by bronchoscopy before they progress to malignant transformation...
  15. ncbi Gene profiling of normal human bronchial epithelial cells in response to asbestos and benzo(a)pyrene diol epoxide (BPDE)
    Ilana Belitskaya-Levy
    Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    J Environ Pathol Toxicol Oncol 26:281-94. 2007
    ..These in vitro findings in NHBE cells model environment-gene interaction for asbestos and BPDE, highlighting effects of inflammation, fibrosis, proliferation, and DNA damage recognition and repair...
  16. pmc Detection of lung cancer using weighted digital analysis of breath biomarkers
    Michael Phillips
    Menssana Research Inc, Fort Lee, NJ 07024 6510, United States
    Clin Chim Acta 393:76-84. 2008
    ..We developed a non-linear method of multivariate analysis, weighted digital analysis (WDA), and evaluated its ability to predict lung cancer employing volatile biomarkers in the breath...
  17. pmc Performance of mitochondrial DNA mutations detecting early stage cancer
    John P Jakupciak
    Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA
    BMC Cancer 8:285. 2008
    ..The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites...
  18. pmc Wnt pathway in pulmonary fibrosis in the bleomycin mouse model
    Li Liu
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Environ Pathol Toxicol Oncol 28:99-108. 2009
    ..The Wnt/beta-catenin signaling pathway plays an important role in regulating cellular differentiation, proliferation, and polarity...
  19. pmc Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung disease
    Michael K Showe
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Cancer Res 69:9202-10. 2009
    ..Our results show the feasibility of using peripheral blood gene expression signatures to identify early-stage NSCLC in at-risk populations...
  20. pmc Emerging exposures and respiratory health: World Trade Center dust
    William N Rom
    MPH, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 1st Ave, New York, NY 10016, USA
    Proc Am Thorac Soc 7:142-5. 2010
    ....
  21. pmc Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers
    William N Rom
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Radiology, Thoracic Surgery, and Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA
    BMC Cancer 10:234. 2010
    ..Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways...
  22. pmc Molecular analysis of plasma DNA for the early detection of lung cancer by quantitative methylation-specific PCR
    Kimberly Laskie Ostrow
    Department of Otolaryngology Head and Neck Cancer Research Division, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA
    Clin Cancer Res 16:3463-72. 2010
    ..We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan...
  23. pmc Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs
    Leopoldo N Segal
    Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Human Microbiome Program, New York University School of Medicine, New York, New York
    Ann Am Thorac Soc 11:108-16. 2014
    ..Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. ..

Research Grants30

  1. Genome Wide Association Study of Head and Neck Cancer
    Sanjay Shete; Fiscal Year: 2013
    ....
  2. The Emphysematous Microenvironment Promotes Lung Tumorigenesis and Progression
    John J Reilly; Fiscal Year: 2013
    ....
  3. Factors for Epigenetic Silencing of Lung Cancer Genes
    Steven A Belinsky; Fiscal Year: 2013
    ..Therefore, these studies will identify biomarkers for risk assessment and early detection of lung cancer, the leading cause of cancer-related death in the U.S. ..
  4. Epigenetic Changes Link COPD and Lung Cancer
    Yohannes Tesfaigzi; Fiscal Year: 2013
    ..Together, the integrated results from these studies will provide novel insights into mechanisms that connect COPD to the development of lung cancer. ..
  5. Biosynthesis and Function of Lactosaminyl Glycans in Hematopoiesis
    Robert Sackstein; Fiscal Year: 2013
    ..This research effort should yield new treatments to improve marrow function in such conditions. (End of Abstract) ..
  6. Early detection of lung cancer in veterans
    Feng Jiang; Fiscal Year: 2013
    ..The use of the biomarkers that can identify NSCLC at its early stage will offer the best opportunity for effective treatments of the malignancy, and therefore will provide the best health care for Veterans diagnosed with lung cancer. ..
  7. Identifying non-coding RNAs for early detection and prevention of lung cancer
    Harvey Ira Pass; Fiscal Year: 2013
    ....
  8. Frontotemporal Dementias: Genotypes and Phenotypes
    Virginia M Lee; Fiscal Year: 2013
    ..elegans and transgenic mouse models. The proposed studies will provide important insights into mechanisms of FTLD and the diagnosis and treatment of these disorders. ..
  9. Benefits and Harms of Lung Cancer Screening in HIV Infection
    Juan P Wisnivesky; Fiscal Year: 2013
    ....