Meng Xu, Penghui Hu, Ling Jin

Department of Oncology, The First Affiliated of Jinan University, Guangzhou.

Objective: Lungcancer is the leading cause of cancer-related deaths in China, currently, lung adenocarcinoma has become the major pathologic type of lung cancer. Multidrug resistance (MDR) is a major problem in cancer eradication by reducing chemotherapy efficacy. However, it still remains unclear whether chemotherapy affects driven genes status in lung adenocarcinoma. A better understanding of MDR and driven genes biology in lung adenocarcinonoma may real new molecular targets for successful lung cancer treatment. The purpose of our study was to determine the relationship between MDR and driven genes in lung adenocarcinoma. Method: Transcriptomes for lung adenocarcinoma tissue samples were produced using the Illumina Hiseq 2000 platform. Diferentially expressed genes between drug sensitive and drug resistant samples were detected using Expectation-Maximization (RSEM) and Poisson distribution analysis. Result: A total of 54,532,764 and 51,838,982 pair-end reads were generated for drug sensitive and drug resistant lung adenocarcinoma tissue samples, respectively. 65.08% and 76.31% clean reads were successfully mapped to the human reference genome (hg19). The numbers of expressed genes detected in drug sensitive and drug resistant lung adenocarcinoma tissue samples were 17,300 and 16,422. Compared with drug sensitive sample, there were 6002 differentially expressed genes indrug resistant sample, including 3367 up-regulated and 2635 down-regulated ones. In order to investigate drug sensitive and drug resistant lung adenocarcinoma tissue samples expressed on 20 driven genes which might berelated to MDR. These genes were involved in the various pathways, such as angiogenesis, pathogenesis, cell death, cell growth, cell division, cell cycle, cell proliferation, apoptosis process, cell differentiation and drug metabolism. The results showed that 90% (18/20) genes (GSTP1, MET, ROS1, PRKCA,ABCG2, MMP1, ABCB1,VEGFA, KRAS, LRP1, ABCC1, PIK3CA, COX5A, BRAF, EGFR, PTEN, ALK,FGFR1) were up-regulated in drug resistant sample. There were 35% (7/20) genes (GSTP1,MET, ROS1, PRKCA, ABCG2, MMP1, ABCB1) were significantly up-regulated (FDR≤0.001 and |log2 (Fold change) |≥1). Specifically, the exp-ression of ROS1 in drug resistant sample was 227 times higher than that of the drug sensitive adenocarcinoma tissue sample. Conclusion: The expression levels of the driven genes were generally up-regulated and their deregulation may contribute to MDR in lung adenocarcinoma. These findings indicate thatdriver genes play a critical role in drug resistance of lung adenocarcinoma andmay be potential therapeutic targets.

Key Words: Lung cancer  Driven genes  Multidrug resistance