scholarly journals Frequent DNA methylation changes in cancerous and noncancerous lung tissues from smokers with non-small cell lung cancer

Mutagenesis ◽  
2020 ◽  
Author(s):  
Kristina Daniunaite ◽  
Agne Sestokaite ◽  
Raimonda Kubiliute ◽  
Kristina Stuopelyte ◽  
Eeva Kettunen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Methylation Status ◽  
Small Cell ◽  
Study Cohort ◽  
Tumour Suppressor Genes ◽  
Epigenetic Changes ◽  
Small Cell Lung ◽  
Specific Pcr ◽  
Never Smokers

Abstract Cancer deaths account for nearly 10 million deaths worldwide each year, with lung cancer (LCa) as the leading cause of cancer-related death. Smoking is one of the major LCa risk factors, and tobacco-related carcinogens are potent mutagens and epi-mutagens. In the present study, we aimed to analyse smoking-related epigenetic changes in lung tissues from LCa cases. The study cohort consisted of paired LCa and noncancerous lung tissues (NLT) from 104 patients, 90 of whom were smokers or ex-smokers (i.e. ever smokers) at the time of diagnosis. DNA methylation status of tumour suppressor genes DAPK1, MGMT, p16, RASSF1 and RARB was screened by means of methylation-specific PCR (MSP) and further analysed quantitatively by pyrosequencing. Methylation of at least one gene was detected in 59% (61 of 104) of LCa samples and in 39% (41 of 104) of NLT. DAPK1 and RASSF1 were more frequently methylated in LCa than in NLT (P = 0.022 and P = 0.041, respectively). The levels of DNA methylation were higher in LCa than NLT at most of the analysed CpG positions. More frequent methylation of at least one gene was observed in LCa samples of ever smokers (63%, 57 of 90) as compared with never smokers (36%, 5 of 14; P = 0.019). In the ever smokers group, methylation of the genes also occurred in NLT, but was rare or absent in the samples of never smokers. Among the current smokers, RASSF1 methylation in LCa showed association with the number of cigarettes smoked per day (P = 0.017), whereas in NLT it was positively associated with the duration of smoking (P = 0.039). Similarly, p16 methylation in LCa of current smokers correlated with the larger number of cigarettes smoked per day (P = 0.047). Overall, DNA methylation changes were present in both cancerous and noncancerous tissues of LCa patients and showed associations with smoking-related parameters.

scholarly journals Detection of SHOX2 DNA methylation by methylation-specific PCR in non-small cell lung cancer

2020 ◽  
Vol 9 (10) ◽  
pp. 6070-6077
Author(s):  
Hongxiang Feng ◽  
Weipeng Shao ◽  
Lanfang Du ◽  
Xin Qing ◽  
Zhenrong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Methylation Specific Pcr ◽  
Specific Pcr

PP255 Epigenetic Profile Predicts Response To Immunotherapy In Patients With Non-Small-Cell Lung Cancer: An Early Assessment

2020 ◽  
Vol 36 (S1) ◽  
pp. 22-22
Author(s):  
Ana Isabel Hijas-Gómez ◽  
Mª Mar Polo-de-Santos ◽  
Setefilla Luengo-Matos ◽  
Montserrat Carmona-Rodríguez ◽  
Luís María Sánchez-Gómez
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Methylation Status ◽  
Small Cell ◽  
Therapeutic Decision ◽  
Small Cell Lung ◽  
Early Assessment ◽  
Cpg Sites ◽  
Therapeutic Decision Making

IntroductionEpigenetics is an innovative discipline that aims to provide biomarkers to aid in early diagnosis, patient risk classification, or outcome prediction. The identification of therapeutic targets is of particular interest in cancer therapy for selecting groups of patients who may benefit most from an intervention. Understanding the relationships between the immune system and tumor cells has led to new immunotherapy-based therapies that provide a promising alternative to conventional cancer therapies. The aim of this study was to conduct an early assessment of a novel epigenetic signature (EPIMMUNE) that could predict response to programmed cell death protein 1 (PD-1) inhibitor immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsWe identified the novel epigenetic signature EPIMMUNE through the Early Awareness and Alert System, “SINTESIS-new technologies” of the Agencia de Evaluación de Tecnologías Sanitarias in Spain (AETS-ISCIII). A literature search of PubMed, Embase, the Web of Science, the Trip database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, The Cochrane Library, and the Centre for Reviews and Dissemination databases was conducted. Clinical studies on EPIMMUNE published in English or Spanish up to August 2019 were reviewed.ResultsOnly one retrospective study was found. Identification of EPIMMUNE was accomplished through interrogation of the DNA methylation status of CpG sites in 142 samples from adult patients with NSCLC who were treated with PD-1 inhibitors. EPIMMUNE was defined by 301 CpG sites whose methylation status was significantly associated with clinical response (progression-free and overall survival). No studies assessing the long-term clinical utility, impact on therapeutic decision making, or economic implications of EPIMMUNE were found.ConclusionsThe EPIMMUNE signature could provide an accurate and valid biomarker for identifying patients with NSCLC who may benefit from treatment with PD-1 inhibitors. However, the technology is under development, and there is only a single study on detecting the EPIMMUNE epigenetic profile and identifying the DNA methylation profiles associated with increased survival after PD-1 inhibitor therapy. More diagnostic accuracy studies and prospective, long-term trials are needed to evaluate the clinical impact this technology may have on therapeutic decision making. Given the limited evidence available, further research is needed before the technology can be disseminated.

scholarly journals Real World Characterization of Advanced Non-Small Cell Lung Cancer in Never Smokers by Actionable Mutation Status

2021 ◽  
Author(s):  
Kathleen Kerrigan ◽  
Xuechen Wang ◽  
Benjamin Haaland ◽  
Blythe Adamson ◽  
Shiven Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutation Status ◽  
Never Smokers

scholarly journals Proportion and clinical features of never-smokers with non-small cell lung cancer

2017 ◽  
Vol 36 (1) ◽  
Author(s):  
Jaeyoung Cho ◽  
Sun Mi Choi ◽  
Jinwoo Lee ◽  
Chang-Hoon Lee ◽  
Sang-Min Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Features ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Never Smokers

Difference in survival and prognostic factors between smokers and never-smokers with advanced non-small-cell lung cancer

2011 ◽  
Vol 18 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Shiro Tanaka ◽  
Kazuhiro Yanagihara ◽  
Satoshi Tamaru ◽  
Satoshi Teramukai ◽  
Toshiyuki Kitano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Never Smokers

scholarly journals Nivolumab in never-smokers with advanced squamous non-small cell lung cancer: Results from the Italian cohort of an expanded access program

Tumor Biology ◽  
2018 ◽  
Vol 40 (11) ◽  
pp. 101042831881504 ◽  
Author(s):  
Marina Chiara Garassino ◽  
Lucio Crinò ◽  
Annamaria Catino ◽  
Andrea Ardizzoni ◽  
Enrico Cortesi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Never Smokers ◽  
Access Program

Objectives: Never-smokers may be a distinct subgroup among patients with advanced non-small cell lung cancer, appearing to benefit less from immunotherapy than smokers. We report results from never-smokers enrolled in the Italian cohort of the nivolumab expanded access program in pre-treated patients with advanced squamous non-small cell lung cancer. Materials and methods: Nivolumab (3 mg/kg every 2 weeks for ≤24 months) was available on physician request. Efficacy data included objective tumor response, date of progression, and survival information. Safety was monitored. Results: Overall, 371 patients received at least one dose of nivolumab, including 31 never-smokers (8%). Objective response rate, disease-control rate, and median overall survival were 23%, 45%, and 12.1 months (95% confidence interval: 3.7–20.4), respectively, in never-smokers, and 18%, 47%, and 7.9 months (95% confidence interval: 6.2–9.6), respectively, in the overall expanded access program population. Any-grade and grade 3–4 treatment-related adverse events were reported in 12 (39%) and 3 (10%) never-smokers, respectively, and in 109 (29%) and 21 (6%) patients, respectively, in the overall expanded access program population. Grade 3–4 treatment-related adverse events in non-smokers were increased transaminases (n = 2; 6%) and diarrhea (n = 1; 3%). Treatment-related adverse events led to treatment discontinuation in 4 non-smokers (17%) and in 26 patients (9%) overall. Conclusion: Pre-treated never-smokers with advanced squamous non-small cell lung cancer in this Italian expanded access program demonstrated efficacy and safety that were consistent with those in the overall expanded access program population and clinical trials. These results suggest that a proportion of never-smoker patients with squamous non-small cell lung cancer may be responsive to immunotherapy. Other factors, such as the tumor mutational load and the status of programmed death-ligand 1, anaplastic lymphoma kinase, and epidermal growth factor receptor, might play a potential key role.

scholarly journals Survival in never-smokers with non-small cell lung cancer: A population-based study from Sweden

2018 ◽  
Vol 29 ◽  
pp. viii489
Author(s):  
L. Löfling ◽  
S. Bahmanyar ◽  
A. Karimi ◽  
H. Kieler ◽  
M. Lambe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Population Based ◽  
Small Cell ◽  
Small Cell Lung ◽  
Population Based Study ◽  
Never Smokers
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