Abstract
Human tissue kallikreins are a family of 15 secreted serine proteases. We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer. Here, we examined the clinical value of 11 members of the tissue kallikrein family as potential biomarkers for lung cancer diagnosis. Serum specimens from 51 patients with non-small cell lung cancer (NSCLC) and from 50 healthy volunteers were collected. Samples were analyzed for 11 kallikreins (KLK1, KLK4-8, and KLK10-14) by specific ELISA. Data were statistically compared and receiver operating characteristic curves were constructed for each kallikrein and for various combinations. Compared with sera from normal subjects, sera of patients with NSCLC had lower levels of KLK5, KLK7, KLK8, KLK10, and KLK12, and higher levels of KLK11, KLK13, and KLK14. Expression of KLK11 and KLK12 was positively correlated with stage. With the exception of KLK5, expression of kallikreins was independent of smoking status and gender. KLK11, KLK12, KLK13, and KLK14 were associated with higher risk of NSCLC as determined by univariate analysis and confirmed by multivariate analysis. The receiver operating characteristic curve of KLK4, KLK8, KLK10, KLK11, KLK12, KLK13, and KLK14 combined exhibited an area under the curve of 0.90 (95% confidence interval, 0.87-0.97). We propose a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy. This model requires validation with a larger series and may be further improved by addition of other biomarkers.
Highlights
Human tissue kallikreins are a family of 15 secreted serine proteases.We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer
KLK5, KLK7, KLK8, KLK10, and KLK12 exhibited a reduced expression level, whereas KLK11, KLK13, and KLK14 were overexpressed in lung cancer patients, compared with samples taken from healthy individuals (Fig. 1)
Among different members of the kallikrein family, KLK13 was of particular interest as it was detected in almost 26% of cancers, as opposed to only 4% of normal individuals
Summary
Human tissue kallikreins are a family of 15 secreted serine proteases.We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer. Conclusions: We propose a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy. This model requires validation with a larger series and may be further improved by addition of other biomarkers. Human tissue kallikreins are a family of 15 highly conserved serine proteases (KLK1-KLK15) encoded by the largest contiguous cluster of protease genes in the human genome. Due to their protease activity and expression in many tissues and cell types, kallikreins have been implicated in a wide range of physiologic functions, ranging from regulation of cell growth to tissue remodeling and skin desquamation. Kallikreins may be directly or indirectly involved in cancer pathogenesis by www.aacrjournals.org
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