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

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.

An individualised signature for predicting response with concordant survival benefit for lung adenocarcinoma patients receiving platinum-based chemotherapy

“…Recently, our study have proved that genes related to a single drug sensitivity could be identified in clinical samples of patients administered with combination ACT, given that the drugs used in combination had no or limited pharmacological antagonism (Tong et al , 2015). In this study, based on the cell lines data for drug resistance, we demonstrated that DE genes between the responders and non-responders predicted by 3-GPS were concordantly correlated with both carboplatin and cisplatin sensitivity, providing a circumstantial evidence of the relevance between 3-GPS and platinum ACT.…”

FBXW4 Acts as a Protector of FOLFOX-Based Chemotherapy in Metastatic Colorectal Cancer Identified by Co-Expression Network Analysis

“…To date, reliable molecular markers for the FOLFOX/CapeOX regimen resistance in CRC patients are still unavailable, especially for the primary resistance Moreover, we analyzed the data in the GEO dataset, and found eight datasets, GSE19860, GSE52735, GSE104645, GSE14095, GSE83889, GSE72968, GSE110785, and GSE69657 were contained CRC patients who received FOLFOX chemotherapy (Watanabe et al, 2011;Li et al, 2013;Estevez-Garcia et al, 2015;Tong et al, 2015;Del et al, 2017;Cherradi et al, 2017;Kwon et al, 2017;Okita et al, 2018;Cherradi et al, 2019). We further analyzed the above datasets, the results demonstrated that the datasets, GSE104645, GSE110785, GSE19860, GSE52735, and GSE14095, including the information about acquired resistance and lacked the primary resistance.…”

In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells

“…ABCB1 amplifications are associated with clinical resistance to PTX (54). PTX-R4 and R5 showed structural variants on chromosome 1, and PTX-R4 show an amplification event on chromosome 17 that encompassed a variety of ABC transporters (ABCA5, 6,8,9,10). No compelling candidate genes were found in CNVs for PTX-R6.…”

“…Current advancement of DNA microarrays, proteomics technology and RNA-sequencing have contributed to the discovery of drug resistance genes and provided new avenues and potential clues to develop new targeted therapies to overcome the drug resistance (7)(8)(9). Gene expression has been more commonly used to predict resistance associated genes (10), however, gene expression data cannot account for mutations which affect protein activity or genetic heterogeneity among patients. Patient genetic heterogeneity can make the task of predicting the allelic changes difficult even with inferred drug resistance mechanisms from known candidates (e.g.…”