Author:
Zhang Ying,You Chao,Pei Yuchen,Yang Fan,Li Daqiang,Jiang Yi-zhou,Shao Zhimin
Abstract
Abstract
Background
We established a radiogenomic model to predict pathological complete response (pCR) in triple-negative breast cancer (TNBC) and explored the association between high-frequency mutations and drug resistance.
Methods
From April 2018 to September 2019, 112 patients who had received neoadjuvant chemotherapy were included. We randomly split the study population into training and validation sets (2:1 ratio). Contrast-enhanced magnetic resonance imaging scans were obtained at baseline and after two cycles of treatment and were used to extract quantitative radiomic features and to construct two radiomics-only models using a light gradient boosting machine. By incorporating the variant allele frequency features obtained from baseline core tissues, a radiogenomic model was constructed to predict pCR. Additionally, we explored the association between recurrent mutations and drug resistance.
Results
The two radiomics-only models showed similar performance with AUCs of 0.71 and 0.73 (p = 0.55). The radiogenomic model had a higher predictive ability than the radiomics-only model in the validation set (p = 0.04), with a corresponding AUC of 0.87 (0.73–0.91).
Two highly frequent mutations were selected after comparing the mutation sites of pCR and non-pCR populations. The MED23 mutation p.P394H caused epirubicin resistance in vitro (p < 0.01). The expression levels of γ-H2A.X, p-ATM and p-CHK2 in MED23 p.P394H cells were significantly lower than those in wild type cells (p < 0.01). In the HR repair system, the GFP positivity rate of MED23 p.P394H cells was higher than that in wild-type cells (p < 0.01).
Conclusions
The proposed radiogenomic model has the potential to accurately predict pCR in TNBC patients. Epirubicin resistance after MED23 p.P394H mutation might be affected by HR repair through regulation of the p-ATM-γ-H2A.X-p-CHK2 pathway.
Funder
National Natural Science Foundation of China
Cancer research program of national cancer center
Youth Medical Talents-Clinical Imaging Practitioner Program
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
5 articles.
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