Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC.

Ercetin Ercetin,Kühnel Kühnel,Delgado Delgado,Wrenger Wrenger,Yuskaeva Yuskaeva,Janciauskiene Janciauskiene,Meister Meister,Jonigk Jonigk,Liu Liu,Korenbaum Korenbaum,Richtmann Richtmann,Schneider Schneider,Welte Welte,Winter Winter,Muley Muley,Warth Warth,Deluca Deluca,Gomez-Mariano Gomez-Mariano

doi:10.3390/cancers11091306

Abstract

High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.

Highlights

Lung cancer is divided in non-small cell lung cancer (NSCLC, 85% of all lung cancers) and small cell lung cancer (SCLC, 15% of all lung cancers)
SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer or just reflect inflammatory reaction related to cancer development
To get an insight of SERPINA1 expression in NSLC, in a first step, SERPINA1 gene expression was analyzed in a cohort of tumor and adjacent non-tumor tissues of the lung obtained from 351 patients (Table 1)

Summary

Introduction

Lung cancer is divided in non-small cell lung cancer (NSCLC, 85% of all lung cancers) and small cell lung cancer (SCLC, 15% of all lung cancers). NSCLC can be further classified into the main histological groups such as large-cell neuroendocrine carcinoma (LCNEC), squamous cell carcinoma. Lung cancer is a leading cause of cancer-related death worldwide [2] because the majority of patients are diagnosed at a late-stage of the disease, making successful treatment more difficult and survival outcomes poor [3]. Invasiveness and metastasis are major threats to successful treatment of lung cancer. The treatments for lung cancer have improved recent years, and the identification of prognostic factors is of great importance because they can contribute to clinical decision making and help to individualize treatments for this heterogeneous patient population

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