Overexpression of Osteopontin, αvβ3 and Pim-1 Associated with Prognostically Important Clinicopathologic Variables in Non-Small Cell Lung Cancer

Yi Jin,Da-yue Tong,Chun-kui Shao,Jian-yong Yang,Jian-ning Chen,Jia-ping Li,Zhi-ying Feng,Rossella Rota

doi:10.1371/journal.pone.0048575

Abstract

In this study, we examined the expression of osteopontin (OPN), αvβ3 and Pim-1 in non-small cell lung cancer (NSCLC) and investigated the potential clinical implications of their expression patterns in NSCLC. Immunohistochemical assays were used to examine the protein expression of OPN, αvβ3 and Pim-1 in 208 NSCLC samples and their adjacent normal lung tissue specimens. Statistical analyses were performed to evaluate the relationships between OPN, αvβ3 and Pim-1 expression patterns, and their association with the clinical-pathological parameters of NSCLC patients. In NSCLC tissues, the positive rates of OPN, αvβ3 and Pim-1 expression were 67.8% (141/208), 76.0% (158/208) and 58.7% (122/208), respectively. However, in the adjacent normal lung tissues, the positive rates of OPN, αvβ3 and Pim-1 were 20.2% (42/208), 24.0% (50/208) and 14.9% (31/208), respectively. The differences in the positive expression rates of OPN, αvβ3 and Pim-1 between NSCLCs and the adjacent normal lung tissues were all significant (P<0.01). Additionally, the positive expression of OPN, αvβ3 and Pim-1 in NSCLCs was associated with an increase in pathological grade, lymph node metastasis and advanced clinical stage (all P<0.01). Furthermore, associations between the expression of OPN and αvβ3, OPN and Pim-1, and αvβ3 and Pim-1 were also observed in our NSCLC cohort (all P<0.01). The OPN, αvβ3 and Pim-1 proteins are frequently overexpressed in NSCLC and are associated with some clinicopathologic variables that are of known prognostic importance in NSCLC, suggesting that they may play an important role in the development and/or progression of NSCLC.

Highlights

Primary bronchogenic carcinomas of the lung have the highest mortality rate of any malignant tumor in the world, and non-small cell lung cancer (NSCLC) accounts for 85% of primary lung cancers
Recent studies have indicated that OPN is involved in NSCLC progression and metastasis through its interaction with the avb3 integrin receptor, and OPN overexpression in NSCLC is associated with the pathological stage of the tumor, which is one of the predictor of poor prognosis [5]
Further analyses demonstrated that the expression of OPN was significantly associated with the tumor differentiation degree, lymph node metastasis and clinical staging in NSCLC patients (P,0.01)

Summary

Introduction

Primary bronchogenic carcinomas of the lung have the highest mortality rate of any malignant tumor in the world, and non-small cell lung cancer (NSCLC) accounts for 85% of primary lung cancers. Osteopontin (OPN) is a multifunctional secreted phosphorylated glycoprotein that promotes cellular chemotaxis, adhesion and migration These processes mediate the invasion and metastasis of tumor cells and are associated with the occurrence, development, metastasis and prognosis of a variety of cancer types [2,3,4]. The heparinbinding avb integrin mediates cell-cell and cell-matrix adhesion, regulates intracellular signaling pathways and induces the activation of protein-dissolving enzymes, thereby contributing to extracellular matrix and basement cell membrane degradation and promoting the invasion and migration of tumor cells [6]. OPN acts through avb integrin, which in turn activates the FAK, PI3K, Akt, ERK, NF-kB and Pim-1 pathways, contributing to the migration of lung cancer cells [8]. The expression dynamics of OPN, avb and Pim-1 in NSCLCs and their potential biological roles in the tumorigenesis of NSCLC have not been fully elucidated

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Results

Conclusion