Clinical relevance of the multidrug resistance‑associated protein 1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Hu,Penghui; Wong,Patrick  Ting‑Yat; Zhou,Qinghua; Sheng,Lianghe; Niu,Wenbo; Chen,Size; Xu,Meng; Lin,Yiguang

doi:10.3892/or.2018.6652

Clinical relevance of the multidrug resistance‑associated protein 1 gene in non‑small cell lung cancer: A systematic review and meta‑analysis

Authors:
- Penghui Hu
- Patrick Ting‑Yat Wong
- Qinghua Zhou
- Lianghe Sheng
- Wenbo Niu
- Size Chen
- Meng Xu
- Yiguang Lin
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Affiliations: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA, Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, P.R. China
Published online on: August 17, 2018 https://doi.org/10.3892/or.2018.6652
Pages: 3078-3091

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Abstract

The multidrug resistance‑associated protein 1 (MRP1) gene has been found to be consistently overexpressed in the majority of patients with non‑small cell lung cancer (NSCLC). MRP1 is known for its ability to actively decrease intracellular drug concentration, limiting the efficacy of cancer chemotherapy; however, data on the clinical relevance of MRP1 is inconclusive. In the present meta‑analysis, all available published data were combined to provide an updated view on the clinicopathological relevance of MRP1 in patients with NSCLC. A systematic search was conducted to obtain relevant studies published in English, Chinese and Japanese databases. All data from patients with NSCLC who underwent testing for MRP1, by either immunohistochemistry or reverse transcription‑polymerase chain reaction, were extracted and combined for further analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each selected study, with either the fixed‑effects model or the random‑effects model where appropriate. The quality of methodology, heterogeneities and publication bias of the included articles were also analyzed. A total of 36 clinical studies involving 3,278 patients were included in the study. It was found that the increased expression of the MRP1 gene was associated with the following subgroups of patients: Non‑smokers vs. smokers (OR, 2.54; 95% CI, 1.17‑5.54; P=0.019); adenocarcinoma vs. squamous cell carcinoma (OR, 1.58; 95% CI, 1.16‑2.17; P=0.004); clinical stage III‑IV vs. stage I‑II (OR, 1.36; 95% CI, 1.11‑1.66; P=0.003); lymph node metastases (OR, 1.32; 95% CI, 1.09‑1.61; P=0.005); poor response to chemotherapy (OR, 0.41; 95% CI, 0.23‑0.72; P=0.002) and reduced 3‑year survival rate (OR, 0.40; 95% CI, 0.23‑0.68; P=0.001). In conclusion, the findings from this study suggest that increase in MRP1 gene expression is associated with being a non‑smoker, adenocarcinoma, advanced clinical stages and a poor response to chemotherapy in patients with NSCLC. The results from the most extensive and updated data on MRP1 support the requirement for continued investigation into the potential use of MRP1 as a biomarker/clinical indicator for NSCLC.

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