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Eosinophil peroxidase over-expression predicts the clinical outcome of patients with primary lung adenocarcinoma.

ABSTRACT: Eosinophil peroxidase (EPO), a heme protein abundantly expressed in eosinophils, involves in the catalysis of cytotoxic oxidants associated with the pathogenesis of cancer, asthma, and allergic inflammatory disorders. To date, its roles in the pathogenesis of lung cancer are still not known. We determined the expression of EPO in the lung adenocarcinoma tissues and the normal adjacent lung tissues using Real-time PCR and Western blotting analysis, respectively. Also, EPO protein expression in 90 lung adenocarcinoma (AD) samples were confirmed with immunohistochemistry (IHC) using tissue microarrays. Meanwhile, we investigated the association between EPO and the clinicopathological characteristics and disease prognosis in the pulmonary adenocarcinoma patients, which demonstrated that EPO mRNA and protein were significantly higher in lung AD tissues that those of the adjacent normal lung tissues (P<0.05). EPO overexpression was significantly correlated with pathologic-tumour nodes metastasen stage (p-TNM stage, P=0.017) and lymph node metastasis (P=0.027). Patients with EPO overexpression showed shorter survival time than those with low EPO levels (P=0.017), according to the Kaplan-Meier survival curve. Furthermore, a multivariate Cox regression model was utilized to analyze the prognostic factors, which indicated that N stage (HR=0.965, 95% CI=0.328-1.359, P=0.008), p-TNM Stage (HR=3.127, 95% CI =2.463-5.015, P=0.021) and high EPO protein expression (HR=3.145, 95% CI=2.016-5.519, P=0.018) were independent factors for the prognosis of lung AD. In conclusion, increased EPO expression could be used as a biomarker for lung AD patients with poor prognosis.

SUBMITTER: Ye L

PROVIDER: S-EPMC6400814 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Eosinophil peroxidase over-expression predicts the clinical outcome of patients with primary lung adenocarcinoma.

Ye Liang L Wang Hongying H Li Huijuan H Liu Hongbing H Lv Tangfeng T Song Yong Y Zhang Fang F

Journal of Cancer 20190129 4

Eosinophil peroxidase (EPO), a heme protein abundantly expressed in eosinophils, involves in the catalysis of cytotoxic oxidants associated with the pathogenesis of cancer, asthma, and allergic inflammatory disorders. To date, its roles in the pathogenesis of lung cancer are still not known. We determined the expression of EPO in the lung adenocarcinoma tissues and the normal adjacent lung tissues using Real-time PCR and Western blotting analysis, respectively. Also, EPO protein expression in 90 ...[more]

PMID: 30854109

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Project description:Lung cancer is the most common cause of cancer-related deaths in both men and women, accounting for one-quarter of total cancer-related mortality globally. Lung adenocarcinoma is the major subtype of non-small cell lung cancer (NSCLC) and accounts for around 40% of lung cancer cases. Lung adenocarcinoma is a highly heterogeneous disease and patients often display variable histopathological morphology, genetic alterations, and genomic aberrations. Recent advances in transcriptomic and genetic profiling of lung adenocarcinoma by investigators, including our group, has provided better stratification of this heterogeneous disease, which can facilitate devising better treatment strategies suitable for targeted patient cohorts. In a recent study we have shown gene expression profiling identified novel clustering of early stage LUAD patients and correlated with tumor invasiveness and patient survival. In this study, we focused on copy number alterations in LUAD patients. SNP array data identified amplification at chromosome 12q15 on MDM2 locus and protein overexpression in a subclass of LUAD patients with an invasive subtype of the disease. High copy number amplification and protein expression in this subclass correlated with poor overall survival. We hypothesized that MDM2 copy number and overexpression predict response to MDM2-targeted therapy. In vitro functional data on a panel of LUAD cells showed that MDM2-targeted therapy effectively suppresses cell proliferation, migration, and invasion in cells with MDM2 amplification/overexpression but not in cells without MDM2 amplification, independent of p53 status. To determine the key signaling mechanisms, we used RNA sequencing (RNA seq) to examine the response to therapy in MDM2-amplified/overexpressing p53 mutant and wild-type LUAD cells. RNA seq data shows that in MDM2-amplified/overexpression with p53 wild-type condition, the E2F → PEG10 → MMPs pathway is operative, while in p53 mutant genetic background, MDM2-targeted therapy abrogates tumor progression in LUAD cells by suppressing epithelial to mesenchymal transition (EMT) signaling. Our study provides a potentially clinically relevant strategy of selecting LUAD patients for MDM2-targeted therapy that may provide for increased response rates and, thus, better survival.

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Eosinophil peroxidase over-expression predicts the clinical outcome of patients with primary lung adenocarcinoma.

Publications

Eosinophil peroxidase over-expression predicts the clinical outcome of patients with primary lung adenocarcinoma.

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