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  • Title: Prognostic implications of the co-detection of the urokinase plasminogen activator system and osteopontin in patients with non-small-cell lung cancer undergoing radiotherapy and correlation with gross tumor volume.
    Author: Ostheimer C, Evers C, Bache M, Reese T, Vordermark D.
    Journal: Strahlenther Onkol; 2018 Jun; 194(6):539-551. PubMed ID: 29340706.
    Abstract:
    BACKGROUND: The urokinase plasminogen activator system (uPA, uPAR, PAI‑1) is upregulated in cancer and high plasma levels are associated with poor prognosis. Their interaction with hypoxia-related osteopontin (OPN) which is also overexpressed in malignant tumors suggests potential clinical relevance. However, the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell lung cancer (NSCLC), particularly in combination with OPN, has not been investigated so far. METHODS: uPA, uPAR, PAI‑1 and OPN plasma levels of 81 patients with locally advanced or metastasized NSCLC were prospectively analyzed by ELISA before RT and were correlated to clinical patient/tumor data and prognosis after RT. RESULTS: uPAR plasma levels were higher in M1; uPA and PAI‑1 levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p < 0.001) which also correlated with PAI‑1 (p < 0.001). The prognostic impact of OPN plasma levels in the RT of NSCLC was previously reported by our group. PAI‑I plasma levels significantly impacted overall (OS) and progression-free survival (PFS). Low PAI‑1 levels were associated with a significantly reduced OS and PFS with a nearly 2‑fold increased risk of death (p = 0.029) and tumor progression (p = 0.029). In multivariate analysis, PAI‑1 levels remained an independent prognostic factor for OS and PFS with a 3‑fold increased risk of death (p = 0.001). If PAI‑1 plasma levels were combined with OPN or tumor volume, we found an additive prognostic impact on OS and PFS with a 2.5- to 3‑fold increased risk of death (p = 0.01). CONCLUSION: Our results suggest that PAI-1 but not uPA and uPAR might add prognostic information in patients with advanced NSCLC undergoing RT. High pretreatment PAI-1 plasma levels were found predominantly in M0-stage patients and indicate a favorable prognosis as opposed to OPN where high plasma levels are associated with poor survival and metastasis. In combination, PAI-1 and OPN levels successfully predicted outcome and additively correlated with prognosis. These findings support the notion of an antidromic prognostic impact of OPN and PAI-1 plasma levels in the RT of advanced NSCLC.
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