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A Multiparametric Serum Kallikrein Panel for Diagnosis of Non–Small Cell Lung Carcinoma

Authors' Affiliations: ¹ Department of Laboratory Medicine and Pathobiology, University of Toronto and ² Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; ³ Fred Hutchinson Cancer Research Center, Seattle, Washington; ⁴ Divisions of Hematology and Medical Oncology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California; and ⁵ Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

Requests for reprints: Lee Goodglick, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, Box 951732, CHS, Los Angeles, CA 90095-1747. Phone: 310-825-9134; Fax: 310-267-2104; E-mail: lgoodglick{at}mednet.ucla.edu.

Purpose: 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.

Experimental Design: 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.

Results: 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).

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.