Abstract 4425: Multiple -omic analyses of a pair of primary HCC tumor cell lines with different drug response revealed the mechanisms of drug resistance

Abstract

Previously we reported the establishment of a pair of primary HCC cell lines from LIX-004, a patient-derived HCC xenograft model. LIXC004-NA was developed from an untreated PDX tumor; LIXC004-SR was generated from a PDX tumor progressed despite long term in vivo treatment with sorafenib. The two cell lines displayed similar response to sorafenib treatment in vitro. However, LIXC004-NA is sensitive and LIXC004-SR is resistant to sorafenib treatment in vivo. IHC and in vitro functional studies revealed activation of alternative angiogenic pathways as one of the potential reasons for the sorafenib resistance of LIXC004-SR. To fully explore different mechanisms/pathways, we performed a) micro-array analyses; b) whole exome sequencing; c) RNA-seq analyses of the two cell lines; d) metabolomic analyses of the cell lines in vitro culture in the presence and absence of different therapeutics; e) RNAseq analyses of the tumors derived from these two cell lines. The combination of different types of -omic analyses is our systematic approach to address the potential mechanisms of drug resistance without bias. The two cell lines shared a lot of the genetic mutation and expression profile for most genes. Differentially mutated or expressed genes were also identified at basal level. More changes were observed with the treatment of different therapeutics as well as analyses of the xenograft derived from the cell lines. Pathway analyses are performed to explore the underlying mechanisms for the development of drug resistance. Citation Format: Gang Hu, Alicia Du, Yong Huang, Kunyan Liu, Fubo Xie, Xuzhen Tang, Xueyan Yang, Qi Gu, Yixin Zhang, Weikang Tao, Yingjia Zhang, Wei Tang, He Zhou. Multiple -omic analyses of a pair of primary HCC tumor cell lines with different drug response revealed the mechanisms of drug resistance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4425. doi:10.1158/1538-7445.AM2015-4425