Loss of expression rather than cytoplasmic mislocalization of RUNX3 predicts worse outcome in non-small cell lung cancer

Chen,Xiaohui; Deng,Yujie; Shi,Yi; Zhu,Weifeng; Cai,Yibin; Xu,Chunwei; Zhu,Kunshou; Zheng,Xiongwei; Chen,Gang; Xie,Qi; Weng,Guoxing

doi:10.3892/ol.2018.7993

Loss of expression rather than cytoplasmic mislocalization of RUNX3 predicts worse outcome in non-small cell lung cancer

Authors:
- Xiaohui Chen
- Yujie Deng
- Yi Shi
- Weifeng Zhu
- Yibin Cai
- Chunwei Xu
- Kunshou Zhu
- Xiongwei Zheng
- Gang Chen
- Qi Xie
- Guoxing Weng
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Affiliations: Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China, Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, P.R. China, Department of Cardiac Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
Published online on: February 8, 2018 https://doi.org/10.3892/ol.2018.7993
Pages: 5043-5055
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Functional inactivation of human runt‑related transcription factor 3 (RUNX3) through mutation or epigenetic silencing has been well-documented in many cancerous entities. In addition to gene mutation and promoter hypermethylation, cytoplasmic mislocalization has emerged as another major manifestation of RUNX3 dysfunction in malignancies including breast, colorectal and gastric cancers. The aim of the present study was to investigate whether patients with non‑small cell lung cancer (NSCLC) and different RUNX3 expression patterns would have different overall survival (OS), and the associations between different patterns of clinicopathological parameters and clinical outcome. Expressions of RUNX3 and Ki‑67 were immunohistochemically detected in normal lung tissue (n=5) and surgically resected tissues from NSCLC patients (n=188). The optimal cutoff of RUNX3 was determined by X‑tile software associated with their survival. Apoptotic index in cancerous tissue was evaluated using the terminal deoxynucleotidyl transferase mediated dUTP‑biotin nick end labelling method. The prognostic significance of different expression patterns of RUNX3 was determined by means of Kaplan‑Meier survival estimates and log‑rank tests. It was revealed that loss of RUNX3 expression in NSCLC was correlated with a low cancerous apoptotic index (P<0.001), shorter OS and worse prognosis (P=0.0142), while no statistical difference of apoptotic index (P=0.73) or survival (P=0.3781) was determined between patient subgroups with different localization of RUNX3 expression, which was quite different from the situation demonstrated in other malignancies. In conclusion, loss of expression rather than cytoplasmic mislocalization of RUNX3 predicted worse outcome in NSCLC, which was quite different from what manifested in other cancer types, and thus, the underlying mechanism may deserve further investigation.

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