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

Issue title: Adrenergic Signaling and Cancer: Deciphering the Connections

Guest editors: Amal Melhem-Bertrandtx and Anil K. Soody

Article type: Research Article

Authors: Komatsu, Hiroaki^{a; b} | Kakehashi, Anna^b | Nishiyama, Noritoshi^{a; *} | Izumi, Nobuhiro^a | Mizuguchi, Shinjiro^a | Yamano, Shotaro^b | Inoue, Hidetoshi^{a; b} | Hanada, Shoji^{a; b} | Chung, Kyukwang^{a; b} | Wei, Min^b | Suehiro, Shigefumi^a | Wanibuchi, Hideki^b

Affiliations: [a] Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, Asahi-machi, Abeno-ku, Osaka, Japan | [b] Department of Pathology, Osaka City University Graduate School of Medicine, Asahi-machi, Abeno-ku, Osaka, Japan | [x] Department of Breast medical Oncology, M.D. Anderson Cancer Center, Houston, TX, USA | [y] Department of Gynecologic Oncology, M.D. Anderson Cancer Center, Houston, TX, USA

Correspondence: [*] Corresponding author: Noritoshi Nishiyama, Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Tel.: +81 6 6645 3841; Fax: +81 6 6646 6057; E-mail: m1364552@msic.med.osaka-cu.ac.jp

Abstract: 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.

Keywords: CPLX2, lung neuroendocrine tumor, proteomics, biomarker, prognosis

DOI: 10.3233/CBM-130336

Journal: Cancer Biomarkers, vol. 13, no. 3, pp. 171-180, 2013