Abstract
We performed a pooled analysis of the efficacy of serum neuron-specific enolase (NSE) levels for early detection of small cell lung cancer (SCLC) in patients with benign lung diseases and healthy individuals. Comprehensive searches of several databases through September 2016 were conducted. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Ultimately, 33 studies containing 9546 samples were included in the review. Pooled sensitivity of NSE for detecting SCLC was 0.688 (95%CI: 0.627-0.743), specificity was 0.921 (95%CI: 0.890-0.944), positive likelihood ratio was 8.744 (95%CI: 6.308-12.121), negative likelihood ratio was 0.339 (95%CI: 0.283- 0.405), diagnostic odds ratio was 25.827 (95%CI: 17.490- 38.136) and area under the curve was 0.88 (95%CI: 0.85- 0.91). Meta-regression indicated that study region was a source of heterogeneity in the sensitivity and joint models, while cut-off level was a source in the joint model. Subgroup analysis showed that enzyme linked immunosorbent assays had the highest sensitivity and radioimmunoassay assays had the highest specificity. The diagnostic performance was better in Europe [sensitivity: 0.740 (95%CI: 0.676-0.795), specificity: 0.932 (95%CI: 0.904-0.953)] than in Asia [sensitivity: 0.590 (95%CI: 0.496- 0.678), specificity: 0.901 (95%CI: 0.819-0.948)]. In Europe, 25 ng/ml is likely the most suitable NSE cut-off level. NSE thus has high diagnostic efficacy when screening for SCLC, though the efficacy differs depending on study region, assay method and cut-off level. In the clinic, NSE measurements should be considered along with clinical symptoms, image results and histopathology.
Highlights
Lung cancer is the leading cause of cancer death in China and worldwide for both men and women
Two studies did not report the cut-off positive value of neuron-specific enolase (NSE); the cut-off value greater than or equal to 25 ng/ml were only found in one study, so this subgroup analysis could not conducted in Asian; enzyme linked immunosorbent assays (ELISA): enzyme linked immunosorbent assay; electro-chemiluminescence immunoassays (ECSIA): electro- chemiluminescence immunoassay; radioimmunoassay assays (RIA)= radioimmunoassay assay
NSE, a traditional tumor biomarker, has been well studied over the years [43–45], and it is commonly used in the diagnosis of Small cell lung cancer (SCLC)
Summary
Lung cancer is the leading cause of cancer death in China and worldwide for both men and women. Neuron-specific enolase (NSE) is a glycolytic neurospecific isozyme of enolase [6] This enzyme is a well-established marker whose serum levels are used to support an initial diagnosis of SCLC [7]. Several studies have shown that NSE has a high diagnostic capacity for SCLC patients [8–10]. Enzyme linked immunosorbent assays (ELISA), electro-chemiluminescence immunoassays (ECSIA) and radioimmunoassay assays (RIA) are all used to determine serum NSE levels. This raises uncertainty as to whether the diagnostic efficacy of NSE may differ among the various detecting methods. We conducted a systematic review and meta-analysis to assess the efficacy of serum NSE levels for early detection of SCLC in patients with benign lung diseases and healthy individuals.
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