title: Complexin-2 (CPLX2) as a potential prognostic biomarker in human lung high grade neuroendocrine tumors.
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.
authors.affiliation: Department of Thoracic Surgery, Osaka City University Graduate School of Medicine, Asahi-machi, Abeno-ku, Osaka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Komatsu
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Izumi
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Mizuguchi
authors.forename: Shotaro
authors.initials: S
authors.lastname: Yamano
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Shoji
authors.initials: S
authors.lastname: Hanada
authors.forename: Kyukwang
authors.initials: K
authors.lastname: Chung
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; C095993:complexin II