Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues.

Mengsha Tong,Pan Chi,Qingzhou Guan,Mengyao Li,You Guo,Hao Cai,Xiangyu Li,Zheng Guo,Lu Ao,Weicheng Zheng,Haidan Yan,Xingrong Lu

doi:10.18632/oncotarget.5649

Abstract

Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

Highlights

Expressed genes (DEGs) between parental and drug–induced resistant cells are frequently regarded as drug resistance genes [1,2,3,4,5,6] and used to identify predictive markers of therapeutic benefit [7,8,9]
By analyzing the transcriptional profiles of drug-induced resistant cell models, we showed that basally deregulated (BD) genes mainly reflected drug treatment response and were inconsistent with CRG5-FU/L-OHP
BD genes are significantly consistent with in the parental cells (IP) genes

Summary

Introduction

Expressed genes (DEGs) between parental and drug–induced resistant cells are frequently regarded as drug resistance genes [1,2,3,4,5,6] and used to identify predictive markers of therapeutic benefit [7,8,9]. In contrast to the aforementioned studies, Li et al proposed that DEGs between a drug-induced resistant cell and its parental cell, both of which have undergone drug treatment for a defined time, might represent targets for www.impactjournals.com/oncotarget therapies aimed at reversing drug resistance [19]. We define this type of DEG as inducible difference (ID) genes, which represent the difference between two cell types in response to drug treatment. Given this diversity of definition for candidate drug resistance genes, it is necessary to evaluate the clinical relevance of various genes identified in cell models

Methods

Results

Conclusion