Systematic review and meta-analysis of the efficacy of serum neuron-specific enolase for early small cell lung cancer screening

Lang Huang, Jian-Guo Zhou, Wen-Xiu Yao, Xu Tian, Shui-Ping Lv, Ting-You Zhang, Shu-Han Jin, Yu-Ju Bai and Hu Ma _

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Oncotarget. 2017; 8:64358-64372. https://doi.org/10.18632/oncotarget.17825

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Lang Huang1,*, Jian-Guo Zhou1,*, Wen-Xiu Yao2,*, Xu Tian3, Shui-Ping Lv1, Ting-You Zhang1, Shu-Han Jin4, Yu-Ju Bai1 and Hu Ma1

1Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China

2Department of Oncology, Affiliated Cancer Hospital of Medical School, University of Electronic Science and Technology of China, Sichuan Cancer Hospital and Institute & Cancer, The Second People’s Hospital of Sichuan Province, Chengdu 610000, China

3Chongqing Cancer Hospital and Institute, Chongqing 40030, China

4Department of Cardiology and Endodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi 563000, China

*These authors have contributed equally to this work and should be considered co-first authors

Correspondence to:

Hu Ma, email: [email protected]

Keywords: neuron-specific enolase, diagnosis accuracy, small cell lung cancer, systematic review, meta-analysis

Received: February 13, 2017     Accepted: April 11, 2017     Published: May 11, 2017


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.

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