Frequent transcriptional inactivation of Kallikrein 10 gene by CpG island hypermethylation in non-small cell lung cancer.
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.
Zhang
Youwei
Y
Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Song
Haizhu
H
Miao
Yufeng
Y
Wang
Rui
R
Chen
Longbang
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D014408:Biomarkers, Tumor; C100936:KLK10 protein, human; D007610:Kallikreins