The development of a general drug resistance score model based on MIC50 related gene pairs in colorectal cancer cell lines
Received date: 2020-01-06
Revised date: 2020-04-29
Online published: 2020-05-25
Supported by
Supported by the National Natural Science Foundation of China No(81602738);Young and Middle-Aged Backbone Training Project in the Health System of Fujian Province No(2017-ZQN-56);Fujian Medical University No(2018QH1005)
Cancer cell line models are widely used for testing drug sensitivity and in screening for drug resistance markers. However, the general level of drug resistance in cancer cell lines is often ignored by researchers, making it difficult to apply many drug efficacy markers in clinical practice. In this study, we examined 48 colorectal cancer (CRC) cell lines to calculate the correlation coefficients between the IC50 values for 265 drugs. The general drug resistance evaluation index MIC50 was constructed using the median value of 265 drugs’ IC50 values. Genes with positively correlated expression values and a MIC50 which rose to significance were selected for further study. To analyze the effect of general drug resistance on the response status and prognosis in CRC patients, the general drug resistance scoring model was established based on within-sample relative expression orderings of gene pairs. The results demonstrate that more than 99% of the IC50 correlation coefficients of 265 drugs were significantly positive (FDR<0.05), indicating that CRC cell lines possessed general drug resistance characteristics. Furthermore, we identified 602 general drug resistance related genes, and by using Metascape, we identified four functional modules closely related to tumor resistance. A scoring model of 5-FU-based general drug resistance levels consisting of 21 gene pairs was built. After performing χ 2 test, we found that the general drug resistance level in CRC patients was significantly correlated with the response information after accepting 5-FU-based combination drug therapy. Survival analysis showed that the low scoring cohort of patients had a better prognosis than the higher scoring cohort, indicating that the level of basic drug resistance was closely related to the prognosis and drug response status in these patients. These results provide basic theoretical support for further research on the mechanism of combined chemotherapy resistance and the individualized regimen of clinical drug use in patients with CRC.
Key words： cancer cell lines; general levels of drug resistance; MIC50
Huxing Chen, Lei Xu, Jing Li, Zheng Guo, Lu Ao . The development of a general drug resistance score model based on MIC50 related gene pairs in colorectal cancer cell lines[J]. Hereditas(Beijing), 2020 , 42(6) : 577 -585 . DOI: 10.16288/j.yczz.19-336
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