Algorithm using Neuron-Specific Enolase and Pro-Gastrin-Releasing Peptide to Increase the Diagnostic Accuracy for Small Cell Lung Cancer

Abstract

Dear Editor, Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor that accounts for approximately 15% of all lung cancers [1]. Because cancer cells in SCLC grow rapidly, the cancer likely has invaded other organs by the time symptoms present, which frequently delays initial treatment [2]. Therefore, early detection of SCLC is essential for improving the prognosis. Chest X-ray and computed tomography (CT) are the diagnostic methods of choice in lung cancer. Although low-dose CT is recommended for lung cancer screening in high-risk populations, issues concerning its efficacy, high false-positive rates, overdiagnosis, significant costs, and radiation risk have been raised [3]. Therefore, it is important to focus on harmless biomarkers, and neuron-specific enolase (NSE) has been acknowledged as the most reliable tumor marker for SCLC [4]. Pro-gastrin-releasing peptide (ProGRP) has been used for SCLC screening in Korea since the fully automated ARCHITECT ProGRP immunoassay (Abbott Laboratories, Abbott Park, USA) was introduced in 2012. While ProGRP is a better SCLC marker than NSE [5], it is not as commonly used in clinical practice as NSE. This is likely because of the low serum stability of ProGRP [6]. In the Elecsys ProGRP assay (Roche Diagnostics International, Rotkreuz, Switzerland) that was developed later, the ProGRP-stability issue was solved, and the assay showed clear benefits over the ARCHITECT ProGRP assay [7]. Although numerous studies have compared the validity of various tumor markers in SCLC diagnosis [8-10], no study has presented a practically available tool that uses NSE and ProGRP to increase the diagnostic accuracy. The goal of our study was to create an algorithm to differentiate SCLC from non-small cell lung cancer (NSCLC) using NSE and ProGRP. We prospectively analyzed serum samples from 100 lung cancer patients (age= 67.8±1.0 years, male/female ratio=2.85), including 24 SCLC and 76 NSCLC patients (adenocarcinoma [N=47], squamous cell carcinoma [N=25], large-cell carcinoma [N=3], and adenosquamous carcinoma [N=1]), for NSE and ProGRP. The Institutional Review Board of Kosin University Gospel Hospital, Busan, Korea, approved the study protocol (KUGH 2015-06106). Informed consent was obtained from the patients. NSE (Elecsys NSE, Roche Diagnostics International) and ProGRP (Elecsys ProGRP, Roche Diagnostics International) levels were analyzed using the Cobas e601 module (Roche Diagnostics International). The area under the receiver operating characteristic (ROC)