Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer

Xiaoping Ouyang,1,2 Yumin Huang,2 Xing Jin,3 Wei Zhao,4,5 Tao Hu,2 Feng Wu,2 Jianan Huang1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 3Department of Clinical Laboratory, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China; 4Department of Clinical Biochemistry, School of Laboratory Medicine, Chengdu Medical College, Chengdu, People’s Republic of China; 5Department of Pulmonary Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People’s Republic of China Background: Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy. Purpose: The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC). Patients and methods: OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors. The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC. The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN. Results: Immunostaining indicated that OPN was primarily expressed in the cytoplasm of NSCLC cells. Moreover, OPN correlates with NSCLC clinical traits. The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment. Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis. Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA). Conclusion: The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients. Keywords: osteopontin, non-small-cell lung cancer, clinical outcome, drug resistance, invasion, lactate productio