Frequent epigenetic inactivation of deleted in lung and esophageal cancer 1 gene by promoter methylation in non-small-cell lung cancer.
BACKGROUND
Deleted in lung and esophageal cancer 1 (DLEC1) gene was a new candidate tumor suppressor gene. We determined the expression level and methylation status of DLEC1 in non-small-cell lung cancer (NSCLC), and the DLEC1 methylation in plasma DNA as a biomarker for NSCLC was further evaluated.


METHODS
The study population enrolled 78 paired NSCLC specimens and adjacent normal tissues and 25 benign pulmonary lesions. Meanwhile, corresponding plasma samples were collected. Methylation-specific polymerase chain reaction (PCR) was used to detect the DLEC1 methylation status. DLEC1 gene expression was determined by reverse transcriptase PCR and immunohistochemistry.


RESULTS
Hypermethylation of DLEC1 was found in 41% (32/78) of NSCLC tissues, which was significantly higher than that of adjacent normal tissues (3.8%; 3/78) and benign lesions (0/25; P < .001). Also, DLEC1 methylation was closely correlated with loss of expression, and treatment with 5-aza-2'-deoxycytidine induced DLEC1 restoration in A549 and SPC-A1 cell lines. Furthermore, DLEC1 hypermethylation was associated with advanced stage (P = .011) and lymph node metastasis (P = .019). Methylated DLEC1 was detected in 35.9% (28/78) of plasma samples from NSCLC patients and only 2% (1/50) in cancer-free controls, and the concordance of DLEC1 methylation status in plasmas and corresponding tumor tissues was good.


CONCLUSIONS
DLEC1 is silenced by promoter methylation in NSCLC specimens and is widely expressed in adjacent normal tissues and benign control samples. The high detection rate of methylated DLEC1 in plasma DNA further indicates its potential diagnostic and prognosis values in NSCLC.
Zhang
Youwei
Y
Department of Medical Oncology, Jinling Hospital, Nanjing University, China.
Miao
Yufeng
Y
Yi
Jun
J
Wang
Rui
R
Chen
Longbang
L
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D014408:Biomarkers, Tumor; C119064:DLEC1 protein, human; D025521:Tumor Suppressor Proteins