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Journal of clinical pathology v.70 no.3, 2017년, pp.250 - 254   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

DNA hypermethylation analysis in sputum of asymptomatic subjects at risk for lung cancer participating in the NELSON trial: argument for maximum screening interval of 2 years

Hubers, A Jasmijn (Department of Pathology, VU University Medical Center, , Amsterdam, The Netherlands ) ; Heideman, Danielle A M (Department of Pathology, VU University Medical Center, , Amsterdam, The Netherlands ) ; Duin, Sylvia (Department of Pathology, VU University Medical Center, , Amsterdam, The Netherlands ) ; Witte, Birgit I (Department of Epidemiology and Biostatistics, VU University Medical Center, , Amsterdam, The Netherlands ) ; de Koning, Harry J (Department of Public Health, Erasmus Medical Center, , Rotterdam, The Netherlands ) ; Groen, Harry J M (Department of Pulmonary Diseases, University Medical Center Groningen, , Groningen, The Netherlands ) ; Prinsen, Clemens F M (Department of Pathology, Canisius-Wilhelmina Hospital, , Nijmegen, The Netherlands ) ; Bolijn, Anne S (Department of Pathology, VU University Medical Center, , Amsterdam, The Netherlands ) ; Wouters, Mandy (Department of Pathology, Canisius-Wilhelmina Hospital, , Nijmegen, The Netherlands ) ; van der Meer, Susanne E (Department of Pathology, Canisius-Wilhelmina Hospital, , Nijmegen, The Netherlands ) ; Steenbergen, Renske D M (Department of Pathology, VU University Medical Center, , Amsterdam, The Netherlands ) ; Snijders, Peter J F (Department of Patholog ) ; Uyterlinde, Anne ; Berkhof, Hans ; Smit, Egbert F ; Thunnissen, Erik ;
  • 초록  

    Aims Lung cancer is the major contributor to cancer mortality due to metastasised disease at time of presentation. The current study investigated DNA hypermethylation of biomarkers RASSF1A , APC , cytoglobin, 3OST2, FAM19A4, PHACTR3 and PRDM14 in sputum of asymptomatic high-risk individuals from the NELSON lung cancer low-dose spiral CT screening trial to detect lung cancer at preclinical stage. Methods Subjects were selected with (i) lung cancer in follow-up (cases; n=65), (ii) minor cytological aberrations (controls; n=120) and (iii) a random selection of subjects without cytological aberrations (controls; n=99). Median follow-up time for controls was 80 months. Cut-off values were based on high specificity to assess diagnostic value of the biomarkers. Results RASSF1A may denote presence of invasive cancer because of its high specificity (93% (95% CI 89% to 96%); sensitivity 17% (95% CI 4% to 31%), with best performance in a screening interval of 2 years. The panel of RASSF1A, 3OST2 and PRDM14 detected 28% (95% CI 11% to 44%) of lung cancer cases within 2 years, with specificity of 90% (95% CI 86% to 94%). Sputum cytology did not detect any lung cancers. Conclusions In a lung cancer screening setting with maximum screening interval of 2 years, DNA hypermethylation analysis in sputum may play a role in the detection of preclinical disease, but complementary diagnostic markers are needed to improve sensitivity.


  • 주제어

    LUNG CANCER .   SPUTUM .   PCR .   ONCOGENES.  

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