Evidence map›Paper›PMID 32559455›Full record

ArticleLung cancer (Amsterdam, Netherlands)2020

Identification of novel epigenetic abnormalities as sputum biomarkers for lung cancer risk among smokers and COPD patients.

Mathewos Tessema, Dereje D Tassew, Christin M Yingling, Kieu Do, Maria A Picchi, Guodong Wu, Hans Petersen, Scott Randell, Yong Lin, Steven A Belinsky and 1 more

Open access · greenAbstract read
In one paragraph

Article in Lung cancer (Amsterdam, Netherlands), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 20 citations in OpenAlex.

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  6. High-throughput Mucus Microrheology for Phenotyping and Disease Modeling.bioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Mathewos TessemaLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA. Electronic address: mtessema@LRRI.org.
Dereje D TassewCOPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA; Currently, Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Christin M YinglingLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA.
Kieu DoLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA.
Maria A PicchiLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA.
Guodong WuLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA.
Hans PetersenCOPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Scott RandellDepartment of Cell and Molecular Physiology, The University of North Carolina, Chapel Hill, NC, USA.
Yong LinLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA.
Steven A BelinskyLung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, M, USA.
Yohannes TesfaigziCOPD Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA; Currently, Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: ytesfaigzi@bwh.harvard.edu.
Lovelace Respiratory Research Institute · USBrigham and Women's Hospital · USUniversity of North Carolina at Chapel Hill · US

Funding

RESPIRATORY RESEARCHT32HL007633 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI George R Washko · 1985 to 2026
$14.9M
Resolution of Epithelial Cell Hyperplasia in AsthmaR01HL068111 · NHLBI · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI TESFAIGZI, YOHANNES · 2003 to 2021
$10.9M
Epigenetic Changes Link COPD and Lung CancerR01CA164782 · NCI · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI BELINSKY, STEVEN A, TESFAIGZI, YOHANNES · 2011 to 2014
$3.2M
Wood Smoke and Chronic Mucous HypersecretionR01HL140839 · NHLBI · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI TESFAIGZI, YOHANNES · 2018 to 2021
$2.8M
Aerosol Delivery of Topotecan for Personalized Lung Cancer TherapyR01CA193532 · NCI · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI KUEHL, PHILIP, TESSEMA, MATHEWOS · 2016 to 2020
$2.6M
Biomarkers for Epigenetic Therapy of Lung CancerR21CA161561 · NCI · LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE · PI BAUMAN, JERRY L, TESSEMA, MATHEWOS · 2012 to 2013
$476k
NCI NIH HHS R01 CA164782NCI NIH HHS R01 CA193532NCI NIH HHS R21 CA161561NHLBI NIH HHS R01 HL068111NHLBI NIH HHS R01 HL140839NHLBI NIH HHS T32 HL007633
6 · The paper itself

Abstract

objectivesSmoking is a common risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Although COPD patients have higher risk of lung cancer compared to non-COPD smokers, the molecular links between these diseases are not well-defined. This study aims to identify genes that are downregulated by cigarette smoke and commonly repressed in COPD and lung cancer. MATERIALS AND

methodsPrimary human airway epithelial cells (HAEC) were exposed to cigarette-smoke-extract (CSE) for 10-weeks and significantly suppressed genes were identified by transcriptome array. Epigenetic abnormalities of these genes in lung adenocarcinoma (LUAD) from patients with or without COPD were determined using genome-wide and gene-specific assays and by in vitro treatment of cell lines with trichostatin-A or 5-aza-2-deoxycytidine.

resultsThe ten most commonly downregulated genes following chronic CSE exposure of HAEC and show promoter hypermethylation in LUAD were selected. Among these, expression of CCNA1, SNCA, and ZNF549 was significantly reduced in lung tissues from COPD compared with non-COPD cases while expression of CCNA1 and SNCA was further downregulated in tumors with COPD. The promoter regions of all three genes were hypermethylated in LUAD but not normal or COPD lungs. The reduced expression and aberrant promoter hypermethylation of these genes in LUAD were independently validated using data from the Cancer Genome Atlas project. Importantly, SNCA and ZNF549 methylation detected in sputum DNA from LUAD (52% and 38%) cases were more prevalent compared to cancer-free smokers (26% and 15%), respectively (p < 0.02).

conclusionsOur data show that suppression of CCNA1, SNCA, and ZNF549 in lung cancer and COPD occurs with or without promoter hypermethylation, respectively. Detecting methylation of these and previously identified genes in sputum of cancer-free smokers may serve as non-invasive biomarkers for early detection of lung cancer among high risk smokers including COPD patients.

Indexed as

Lung NeoplasmsPulmonary Disease, Chronic ObstructiveBiomarkersDNA MethylationEpigenesis, GeneticHumansLungSmokersSputumBiomarkersBiomarkersCOPDEpigeneticMethylationNSCLCSputum

Identifiers

PMID32559455
PMCPMC7384485
OpenAlexW3028136900

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.