Complexin-2 (CPLX2) as a potential prognostic biomarker in human lung high grade neuroendocrine tumors

The present study aimed to identify novel useful clinical biomarker of high grade lung neuroendocrine tumors (LNETs). Based on the results of QSTAR LC-MS/MS analysis, we selected complexin-2 (CPLX2) (upregulated 8.7-fold) as a potential biomarker in high grade human LNETs, and validated its expression immunohistochemically in comparison with non-small cell lung carcinomas (NSCLCs). CPLX2 was strongly positive in 16.3% of examined LNETs, but completely negative in all adjacent non-cancerous tissues and NSCLCs. Importantly, positive CPLX2 expression was associated with lymph vessel invasion (P=0.016), pathological stage (P=0.031), and poor disease-specific survival (P=0.004) of patients with LNETs. Preoperative serum CPLX2 level measured by ELISA was significantly elevated in high grade LNETs as compared with %NCs non-cancer controls (NCs) (P=0.002) and NSCLCs (P< 0.001). Receiver operating characteristic (ROC) curve analysis was used for separating high-grade LNET patients from NSCLC patients. The area under the ROC curve (AUC) was 0.825. The calculated optimal cut-off point for CPLX2 level in the serum was 17.8 pg/ml (Youden index=0.591), while sensitivity and specificity was 94.1% and 65.0%, respectively. CPLX2 is suggested as a novel potential clinically useful biomarker for the diagnosis, prognosis and adequate choice of therapy for patients with high grade LNETs.