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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., Patients and 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., Conclusion: 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.

The role of Kallikrein 10 gene (KLK10) in non-small cell lung cancer (NSCLC) remains largely unknown. We determined the frequency and functional significance of KLK10 hypermethylation in NSCLC. The mRNA expression and methylation status of KLK10 in 78 pairs NSCLC specimens was explored. The biological effects of KLK10 were analyzed by transfection. The results showed that, KLK10 was significantly downregulated in NSCLC (57.7%, 45/78) as compared to non-cancer samples (P = 0.010). CpG island hypermethylation of KLK10 was detected in 46.2% (36/78) NSCLC tissues and was closely correlated with loss of transcript (P < 0.001). KLK10 methylation was associated with advanced stage (P = 0.013) and lymph metastasis (P = 0.015). Furthermore, demethylation treatment restored the expression of KLK10 in two lung adencarcinoma cell lines (A549, SPC-A1). Forced expression of KLK10 in A549 and SPC-A1 remarkably suppressed cells proliferation, migration in vitro and oncogenicity in vivo. Additionally, methylated KLK10 was detected in 38.7% (30/78) of plasma samples from cancer patients but rare in cancer-free controls (P < 0.001). In conclusion, KLK10 acts as a functional tumor suppressor gene in NSCLC, epigenetic inactivation of KLK10 is a common event contributing to NSCLC pathogenesis and may be used as a potential biomarker.