Copper-transporting P-type adenosine triphosphatase ATP7A is associated with platinum-resistance in non-small cell lung cancer NSCLCReport as inadecuate




Copper-transporting P-type adenosine triphosphatase ATP7A is associated with platinum-resistance in non-small cell lung cancer NSCLC - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 10:21

Combination strategies

Abstract

BackgroundCopper export protein ATP7A is important for maintaining copper homeostasis. Recent studies have shown that copper transporters are also involved in the transport of platinum. The goal of this study was to determine the role of ATP7A in the platinum-resistance of non-small cell lung cancer NSCLC.

MethodsSensitivities to platinums were detected by MTT assay and drug-resistance related genes were analyzed by real-time PCR and immunoblotting between DDP-sensitive A549 and the corresponding DDP-resistant cell subline A549-DDP. ATP7A expression was evaluated by immunohistochemistry in tumor tissues of unresectable NSCLC patients who received cisplatin-basing chemotherapy.

ResultsThe expression of ATP7A was significantly higher in A549-DDP cell subline than in A549 cells at both mRNA and protein levels. The silencing of ATP7A expression in A549-DDP by siRNA partially reversed DDP-resistance 29.62% and increased cell apoptosis. ATP7A expression was detected in 41.6%of NSCLC patients, but not in adjacent stroma nor normal lung tissues. ATP7A-positive patients had a significantly poorer histological grade p = 0.039 and poorer response to platinum-basing chemotherapy p = 0.001 compared with ATP7A-negative patients. Cox-s proportional hazards analysis showed that ATP7A expression was an independent prognostic factor for overall survival p = 0.045.

ConclusionsATP7A overexpression played an important role in platinum-resistance of NSCLC, and was a negative prognostic factor of NSCLC patients treated with platinum-based chemotherapy.

AbbreviationsATP7AAdenosine triphosphatase

NSCLCNon-small cell lung cancer

RECISTResponse Evaluation Criteria in Solid Tumors

ABCATP-binding cassette

MDRMultidrug resistance

MRP1Multidrug resistance-associated protein 1

LRPLung resistance protein

ABCG2ATP-binding cassette sub-family G member 2 protein

GSTGSH-S-transferase

DNA polβDNA polymerase beta

PIPropidium iodide

PSPerformance status

OSOverall survival. RT-PCR: Reverse Transcriptase-Polymerase Chain Reaction

CEACarcinoembryonic Antigen.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-10-21 contains supplementary material, which is available to authorized users.

Zhuang-hua Li, Miao-zhen Qiu contributed equally to this work.

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Author: Zhuang-hua Li - Miao-zhen Qiu - Zhao-lei Zeng - Hui-yan Luo - Wen-jing Wu - Feng Wang - Zhi-qiang Wang - Dong-sheng Zhang

Source: https://link.springer.com/







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