Low expression of SerpinB2 is associated with reduced survival in lung adenocarcinomas.

Maria Ramnefjell,Christina Aamelfot,Lars A Akslen,Lars Helgeland

doi:10.18632/oncotarget.21456

Maria Ramnefjell, Christina Aamelfot + Show 2 more

Open Access

https://doi.org/10.18632/oncotarget.21456

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Journal: Oncotarget	Publication Date: Oct 3, 2017
Citations: 11	License type: cc-by

Affiliation: Haukeland University Hospital, University of Bergen

Abstract

Lung cancer is a leading cause of cancer deaths worldwide and new biomarkers are of utmost importance. Studies have indicated that the anti-plasminogen activators SerpinB2 and Neuroserpin, and the adhesion molecule L1CAM, have a coordinated impact on development of metastasis. Here, we examined whether expression of these markers was associated with clinico-pathologic characteristics and prognosis in resected non-small cell lung cancer (NSCLC).Surgical specimens from 438 NSCLC patients treated at Haukeland University Hospital, Bergen, Norway (1993-2010) were included (median age 68 years; 213 adenocarcinomas, 135 squamous cell carcinomas, 90 others). Representative tumor sections were stained for SerpinB2, Neuroserpin, and L1CAM.Low expression of SerpinB2 was associated with reduced lung cancer specific survival (LCSS) in adenocarcinomas (p = 0.017), also in stage I (p = 0.031). In contrast, high SerpinB2 was associated with reduced LCSS in stage I squamous cell carcinomas (p = 0.022). Although Neuroserpin and L1CAM showed some associations with clinico-pathologic phenotype, there were no associations with survival. In multivariate survival analysis of adenocarcinomas, low SerpinB2 demonstrated independent prognostic value (HR 1.8, p = 0.008).In summary, low expression of SerpinB2 in lung adenocarcinomas was an independent prognostic factor. In contrast to findings by others, we found no impact of L1CAM on survival. Introduction

Highlights

Lung cancer is a leading cause of cancer deaths worldwide [1], and non-small cell lung carcinoma (NSCLC) comprises around 85% of all cases
To better understand the molecular mechanisms involved, Valiente et al reported that plasminogen activator www.impactjournals.com/oncotarget inhibitors (SerpinB2 and Neuroserpin) protect cancer cells from an apoptotic cascade initiated by the formation of plasmin in the brain stroma, and along with L1CAM, they are crucial for protecting cancer cells and promoting vascular co-option [6]
Neuroserpin was absent in 25 % of all cases combined, most pronounced among adenocarcinomas (p < 0.001) (Table 1)

Summary

Introduction

Lung cancer is a leading cause of cancer deaths worldwide [1], and non-small cell lung carcinoma (NSCLC) comprises around 85% of all cases. Dissemination of cancer cells is a critical feature of tumor progression, and the mechanisms responsible for cancer cells being able to invade adjacent structures and form new tumors in other organs are still not fully understood [2]. Cells in the brain tissue exhibit several defense-mechanisms to prevent metastasis from forming, and only a limited number of cancer cells survive in this environment [4]. Earlier studies have shown that surviving tumor cells keep in close contact with existing brain capillaries growing as sheaths around them, so-called vascular co-option [5]. To better understand the molecular mechanisms involved, Valiente et al reported that plasminogen activator www.impactjournals.com/oncotarget inhibitors (SerpinB2 and Neuroserpin) protect cancer cells from an apoptotic cascade initiated by the formation of plasmin in the brain stroma, and along with L1CAM, they are crucial for protecting cancer cells and promoting vascular co-option [6]

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