GPNMB expression associates with inferior prognosis in patients with small cell lung cancer

Small cell lung cancer (SCLC) is notorious for its early and frequent metastases, which contribute to it as a recalcitrant malignancy. Previously, we found 4 significantly top up-regulated genes in lymph node (LN) metastases tissue when compared with primary tumor by HTG Edge-seq. Among them, Glycoprotein non-metastatic melanoma protein B (GPNMB) was highly expressed in the metastatic lymph node in SCLC. The aim of this study was to investigate the prognostic value and cellular functions of GPNMB in SCLC. Plasma concentration of GPNMB was performed by enzyme-linked immunosorbent assay (ELISA). Clinical characteristic and Overall survival (OS) based on GPNMB concentration was evaluated. Invasion, migration, proliferation and apoptosis ability of SCLC cells were evaluated using migration, matrigel invasion assays, CCK8 assay and flow cytometry respectively. We found that GPNMB was significantly up-regulated in LN than primary SCLC lesions by HTG Edge-seq. 88 patients with SCLC were included in this study. Plasma GPNMB concentration was significantly higher in patients with extensive disease than local disease (P = 0.043). Baseline plasma GPNMB expression was higher in liver metastasis when compared with non-liver metastasis (P = 0.0148), bone metastasis (P = 0.031), brain metastasis (P = 0.035) and non-organ metastasis (P = 0.0045). Patients with high baseline plasma GPNMB had shorter overall survival (OS) (10.32 vs. 16.10 months, P = 0.0299). Importantly, both univariate and multivariate analyses indicated GPNMB higher expression was an independent biomarker for OS (P = 0.040, HR = 0.444). We also found that inhibit GPNMB expression by siRNA significantly suppressed SCLC metastatic and proliferation ability whereas increased apoptosis ability and caused a significant downregulation of vimentin and upregulation of E-cadherin. Our results suggest that expression of GPNMB is associated with metastasis and poor prognosis, and might be served as a novel potential therapeutic target in SCLC.