Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Cancer Sci. 2010 Apr;101(4):934-40. doi: 10.1111/j.1349-7006.2009.01486.x. Epub 2009 Dec 22.
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.
激肽释放酶 10 基因（KLK10）在非小细胞肺癌（NSCLC）中的作用尚不清楚。我们确定了 KLK10 高甲基化在 NSCLC 中的频率和功能意义。研究了 78 对 NSCLC 标本中 KLK10 的 mRNA 表达和甲基化状态。通过转染分析了 KLK10 的生物学效应。结果表明，与非癌样本相比，KLK10 在 NSCLC 中显著下调（57.7%，45/78）（P = 0.010）。在 46.2%（36/78）的 NSCLC 组织中检测到 KLK10 的 CpG 岛高甲基化，与转录本缺失密切相关（P < 0.001）。KLK10 甲基化与晚期（P = 0.013）和淋巴转移（P = 0.015）相关。此外，去甲基化处理可恢复两种肺腺癌细胞系（A549、SPC-A1）中 KLK10 的表达。在 A549 和 SPC-A1 中强制表达 KLK10 可显著抑制细胞体外增殖、迁移和体内致瘤性。此外，在 38.7%（30/78）的癌症患者血浆样本中检测到甲基化 KLK10，但在无癌症对照中很少见（P < 0.001）。总之，KLK10 在 NSCLC 中作为功能性肿瘤抑制基因发挥作用，KLK10 的表观遗传失活是导致 NSCLC 发病机制的常见事件，可作为潜在的生物标志物。
