Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: a promising tool for early detection of COPD and lung cancer in smokers

被引:48
作者
Guzman, Leda [1 ]
Soledad Depix, Maria [2 ]
Maria Salinas, Ana [2 ]
Roldan, Rosa [3 ]
Aguayo, Francisco [4 ]
Silva, Alejandra [2 ]
Vinet, Raul [5 ,6 ]
机构
[1] Pontificia Univ Catolica Valparaiso, Fac Ciencias, Dept Bioquim, Valparaiso, Chile
[2] Univ Santo Tomas, Escuela Tecnol Med, Fac Salud, Santiago, Chile
[3] Hosp San Jose, Unidad Enfermedades Resp, Santiago, Chile
[4] Univ Chile, Fac Med, Inst Ciencias Biomed ICBM, Programa Virol, Santiago 7, Chile
[5] Univ Valparaiso, Fac Farm, Valparaiso, Chile
[6] CREAS, Valparaiso, Chile
关键词
DNA methylation; Sputum; Lung cancer; COPD; OBSTRUCTIVE PULMONARY-DISEASE; NEVER-SMOKERS; SMOKING; HYPERMETHYLATION; INFLAMMATION; ADENOCARCINOMAS; EXPRESSION; MANAGEMENT; BIOMARKER; PLASMA;
D O I
10.1186/1746-1596-7-87
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Background: Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD. Methods: We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups. Results: DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05). Conclusions: We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects. Virtual slides: The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160
引用
收藏
页数:9
相关论文
共 56 条
[1]  
Adonis R Waldo, 2006, Rev. chil. enferm. respir., V22, P7
[2]  
Amigo H, 2006, REV MED CHILE, V134, P1275
[3]   Circulating nucleic acids in plasma or serum [J].
Anker, P ;
Lyautey, J ;
Lederrey, C ;
Stroun, M .
CLINICA CHIMICA ACTA, 2001, 313 (1-2) :143-146
[4]   COPD: current therapeutic interventions and future approaches [J].
Barnes, PJ ;
Stockley, RA .
EUROPEAN RESPIRATORY JOURNAL, 2005, 25 (06) :1084-1106
[5]   Smokers with airway obstruction are more likely to quit smoking [J].
Bednarek, M. ;
Gorecka, D. ;
Wielgomas, J. ;
Czajkowska-Malinowska, M. ;
Regula, J. ;
Mieszko-Filipczyk, G. ;
Jasionowicz, M. ;
Bijata-Bronisz, R. ;
Lempicka-Jastrzebska, M. ;
Czajkowski, M. ;
Przybylski, G. ;
Zielinski, J. .
THORAX, 2006, 61 (10) :869-873
[6]  
Belinsky SA, 2002, CANCER RES, V62, P2370
[7]   Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort [J].
Belinsky, SA ;
Liechty, KC ;
Gentry, FD ;
Wolf, HJ ;
Rogers, J ;
Vu, K ;
Haney, J ;
Kenned, TC ;
Hirsch, FR ;
Miller, Y ;
Franklin, WA ;
Herman, JG ;
Baylin, SB ;
Bunn, PA ;
Byers, T .
CANCER RESEARCH, 2006, 66 (06) :3338-3344
[8]   Modeling INK4/ARF tumor suppression in the mouse [J].
Berger, Justin H. ;
Bardeesy, Nabeel .
CURRENT MOLECULAR MEDICINE, 2007, 7 (01) :63-75
[9]   The new World Health Organization classification of lung tumours [J].
Brambilla, E ;
Travis, WD ;
Colby, TV ;
Corrin, B ;
Shimosato, Y .
EUROPEAN RESPIRATORY JOURNAL, 2001, 18 (06) :1059-1068
[10]  
Brody Jerome S, 2006, Proc Am Thorac Soc, V3, P535, DOI 10.1513/pats.200603-089MS