Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules

Elena Kupert,Paul Succop,Susan M Pinney,Yin Liu,Sandra Starnes,Trudy Macdonald,Marshall Anderson,Jiang Wang,Kathryn Wikenheiser-Brokamp,Zhongyun Dong,Linda Levin,Shan Lu,Pingping Chen

doi:10.1186/1471-2407-11-513

Elena Kupert, Paul Succop + Show 11 more

Open Access

https://doi.org/10.1186/1471-2407-11-513

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Journal: BMC Cancer	Publication Date: Dec 1, 2011
Citations: 80	License type: cc-by

Affiliation: University of Cincinnati Medical Center

Abstract

BackgroundFive-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.MethodsPlasma 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.ResultsWe 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.ConclusionOur 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.

Highlights

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
The levels of plasma sPLA2-IIa are increased in lung cancer patients The means and standard deviations of plasma sPLA2-IIa levels from 96 patients with lung cancer and 29 patients with benign lung nodules (SPNs) from the benign nodulelung cancer cohort (BNLCC) were 3646 ± 407.3 and 1772 ± 306.8 pg/ml, respectively (Table 1 and 2, and see Additional file 1)
The optimum cutoff value of plasma sPLA2-IIa by Receiver Operating Characteristic (ROC) analysis was 2.4 ng/ml, which resulted in 67% sensitivity for predicting T2 stage lung cancer (AUC: 0.86; 95% confidence interval (95% CI): 0.65 ~ 0.96), as compared with 45% sensitivity for predicting T1 stage lung cancer (Table 3a and Figure 2c)

Summary

Introduction

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. There is no convenient and reliable biomarker effective for early diagnosis. One key to improving lung cancer survival is to diagnose it at an earlier stage, given that the 5-year survival rate with stage 1A non-small cell lung cancer (NSCLC) is as high as 73% [2]. Identification of malignant nodules is crucial because they represent a localized and potentially curable form of lung cancer. There is no single inexpensive, convenient, and reliable biomarker proven effective for the diagnosis of lung cancer [12]

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