Kupert et al. BMC Cancer 2011, 11:513 http://www.biomedcentral.com/1471-2407/11/513 R E S E A R C H A R T I C L E Open Access Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules Elena Kupert1, Marshall Anderson1, Yin Liu2, Paul Succop3, Linda Levin3, Jiang Wang2, Kathryn Wikenheiser-brokamp2, Pingping Chen4, Susan M Pinney3, Trudy Macdonald3, Zhongyun Dong4, Sandra Starnes5 and Shan Lu2* Abstract Background: Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer. Methods: Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined. Results: We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis. Conclusion: Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs. Background Lung cancer is the leading cause of cancer death world- wide with 159,390 deaths in the US in 2009. This repre- sents 30% of total cancer deaths [1]. The 5-year survival rate is only 16%, which has not changed in three dec- ades. One key to improving lung cancer survival is to diagnose it at an earlier stage, given that the 5-year sur- vival rate with stage 1A non-small cell lung cancer (NSCLC) is as high as 73% [2]. Advanced imaging tech- nology and widespread availability of low dose spiral * Correspondence: shan.lu@uc.edu 2Department of Pathology, University of Cincinnati College of Medicine, UC Metabolic Diseases Institute, 2120 E. Galbraith Road, Building A, Room 259, Cincinnati, OH 45237-0507, USA Full list of author information is available at the end of the article computed tomography (LDCT) have led to a significant increase in detection of lung nodules [3,4]. The preva- lence of solitary pulmonary nodules (SPNs), (by defini- tion, a SPN is < 3 cm in diameter), is 10 ~ 20% nationwide and up to 61% in the Ohio valley [5]. The majority of these nodules are benign, even among patients at increased risk for lung cancer such as smo- kers. The difficulty lies in the determination of which SPN is malignant. An increase in the size of a SPN by repeated CT scans is currently one important parameter to predict the presence of malignancy [6,7]. SPNs can be challenging to manage and costly to monitor with radiation exposure of repeat CT scans and potential morbidity of biopsy or surgical resection of benign © 2011 Kupert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.