Integrated analysis profiles of long non-coding RNAs reveal potential biomarkers of drug resistance in lung cancer

Abstract

// Wenhua Xue 1, * , Lifeng Li 1, 2, 3, * , Xin Tian 1, * , Zhirui Fan 3 , Ying Yue 2, 7 , Chaoqi Zhang 2, 3 , Xianfei Ding 6 , Xiaoqin Song 4, 5 , Bingjun Ma 1 , Yunkai Zhai 4, 5 , Jingli Lu 1 , Quancheng Kan 1 and Jie Zhao 1, 4, 5 1 Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China 2 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China 3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China 4 Engineering Research Center of Digital Medicine, Zhengzhou 450052, Henan, China 5 Engineering Laboratory for Digital Telemedicine Service, Zhengzhou 450052, Henan, China 6 Department of General ICU, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China 7 Department of Clinical Laboratory, The No.7. People’s Hospital in Zhengzhou, Zhengzhou 450016, Henan, China * These authors have contributed equally to this work Correspondence to: Jie Zhao, email: zhaojiez2016@163.com Quancheng Kan, email: quanchengkan@yeah.net Keywords: lncRNAs, lung cancer, drug resistance, bioinformatics methods Received: December 09, 2016     Accepted: February 28, 2017     Published: March 22, 2017 ABSTRACT Lung cancer is one of the leading causes of cancer-related death. Resistance to chemotherapy and molecularly targeted therapies is a major problem that can contribute substantially to high mortality. The roles of long non-coding RNAs (lncRNAs) in drug resistance of lung cancer are insufficiently understood. Here, we identified a distinct drug resistance-related transcriptional signature and constructed a functional lncRNA-mRNA co-expression network. We found that 34 lncRNAs and 103 mRNAs have differential expression in drug resistance of lung cancer, in which 10 lncRNAs were down regulated and 24 up regulated; 49 mRNAs were down regulated and 54 up regulated. LncRNAs-mRNAs expression network analysis revealed a role for lncRNAs in modulating cancer-related pathways. We also found that two pair lncRNAs and their subnetworks were highly related to drug resistance. NR_028502.1/NR_028505.1 were found differentially co-expressed with nine mRNAs, and highly correlated with better clinical outcome. NR_030725.1/NR_030726.1 co-expressed with eleven mRNAs, and were associated with poor survival in patients with lung cancer. Our work comprehensively identified expression signature of resistance-associated lncRNAs and their inter-regulated mRNAs in lung cancer.