Osteopontin Expression and Prognostic Significance in Non–Small Cell Lung Cancer

Abstract

Purpose:The survival rate of non^small cell lung cancer patients is very low, and knowledge of predictors of outcome is inadequate. To improve the curability of lung cancer, we need to identify new specific molecules involved in tumorigenesis and progression. The purpose of this study was to better define the role of osteopontin in non^small cell lung cancer biology by determining its prognostic significance. Experimental Design: Osteopontin expression was evaluated by immunohistochemistry, as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide series of patients with stage I-IIIA non^small cell lung cancer (207 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumors with low (<20%) from tumors with high (z20%) osteopontin expression. Results: Taking the series of patients as a whole (207 cases), osteopontin expression was associated with neither overall survival (P = 0.14) nor disease-free survival (P = 0.074). However, among patients with at least 6 years of follow-up (163 cases), 6-year overall survival and disease-free survival were significantly reduced if osteopontin expression was high (P = 0.0085 for overall survival, P = 0.0023 for disease-free survival). Moreover, a statistically significant correlation between high levels of osteopontin and shorter overall survival (P = 0.034) and disease-free survival (P = 0.011) in patients with stage I tumors (136 cases) was shown. Conclusions: Our results support the hypothesis of an association between high osteopontin expression and poor survival of patients with stage I non^small cell lung cancer, suggesting that osteopontin could be a candidate target for cancer therapy.Lung cancer is currently the most frequently diagnosed solid tumor in the world as well as the most common cause of cancer mortality worldwide: an estimated 1.2 million people are diagnosed annually with lung cancer and 1.1 million of them die from the disease. Non -small cell lung cancer (NSCLC) comprises >80% of lung cancers, and complete surgical resection of primary tumors in early-stage disease is the only potentially curative treatment. Despite improvements in detection and in surgical and medical treatments during the past two decades, the 5-year survival rate for patients with NSCLC ranges from 9% to 61% following resection depending on clinical stage; survival rates after surgery (pathologic stage) range from 25% to 67%. One area of intense research in early-stage NSCLC regards the identification of molecular markers to complement tumor-node-metastasis staging to fully assess the prognosis of patients and to define innovative strategies (1, 2). Numerous prognostic factors have been identified in patients with early-stage NSCLC that might enable classification of such patients into different subsets corresponding to different risks of recurrence following complete resection.One of the factors that have recently been shown to be linked to cancer development, progression, and metastasis in differen...

Expression of Osteopontin in oesophageal squamous cell carcinoma

“…It has previously been demonstrated that plasma Osteopontin in ESCC is associated with poor survival (Shimada et al, 2005). Expression of Osteopontin is also significantly associated with poor survival in stage I non-small cell lung cancer (Donati et al, 2005). These findings indicate that the Osteopontin overexpression in some tumours is correlated with poor prognosis, predominantly via lymph node metastasis.…”

“…In non-small cell lung cancer, the expression of Osteopontin in surgical specimens is significantly correlated with tumour size, lymph node metastasis and stage (Donati et al, 2005). In the ESCC, plasma Osteopontin was associated with lymph node metastasis (Shimada et al, 2005).…”

“…The expression of Osteopontin has subsequently been demonstrated in a wide range of normal human tissue and body fluid such as osteoblasts, arterial smooth muscle cells, leukocytes, activated macrophages and T cells (Coppola et al, 2004), and epithelia of the gastro-intestinal tract (Brown et al, 1992;Brown et al, 1994). It is a multifunctional protein involved in cell adhesion and cell migration, and has been shown to play important roles in tumorigenesis, tumour invasion, metastasis and prognosis among patients with breast (Tuck et al, 1998), lung (Zhang et al, 2001;Donati et al, 2005), prostate (Thalmann et al, 1999), gastric (Ue et al, 1998) and colon cancer (Agrawal et al, 2002).…”

Prognostic significance of osteopontin expression in non-small-cell lung cancer: A meta-analysis

“…A further 2 studies were excluded [one focused on the association between OPN and bone metastases (17), whereas the other provided limited data on HR and 95% CI (18) and the authors were unavailable for more detailed information]. In addition, after performing an in-depth check of the literature, we found that the same cohort was enrolled in two reports (19,20) and only considered the study by Donati et al (19), which had a larger sample size and included more detailed information. Finally, 6 studies were considered eligible for the meta-analysis, comprising a total of 776 patients (Fig.…”

OPN/CD44v6 overexpression in laryngeal dysplasia and correlation with clinical outcome

“…Expression of the 'v6' variant exon of CD44 is necessary for OPN binding (Ponta et al, 2003). OPN is overexpressed in many human tumours, for example, colon, breast, liver, prostate, gastric, ovarian, lung, thyroid, and kidney carcinomas (Agrawal et al, 2002;Kang et al, 2003;Ye et al, 2003;Schorge et al, 2004;Donati et al, 2005;Guarino et al, 2005;Matusan et al, 2006).…”