| Objective: Neoadjuvant chemotherapy(NAC)plays a pivotal role in the treatment of locally advanced breast cancer(LABC).However,because breast cancer is a heterogeneous disease,individual responses to chemotherapy are highly variable.Therefore,identifying biomarkers that can predict the chemotherapeutic response is crucial.Our aim was to predict the response of NAC by the expression levels of specific mi RNAs in peripheral blood.In addition,we tried to apply bioinformatics and cellular and molecular biology techniques to identify the target genes and mechanisms of the selected mi RNAs,thereby laying a theoretical foundation for its clinical application.Methods: Between March 2014 and January 2016,we recruited 78 primary stage II-III breast cancer patients whose tumours were pathologically confirmed by core needle biopsy and who had received either six or eight cycles of taxane-and anthracycline-based NAC.These patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumours(RECIST)criteria.The Agilent Human mi RNA microarray 21.0 was used to identify differentially expressed candidate mi RNAs in serum samples from the two groups.In addition,to further evaluate the association of relative mi R-4530 expression levels with the response to NAC,we performed quantitative real time-polymerase chain reaction(q RT-PCR).Differences in the clinical characteristics of the patients in resistant and sensitive groups were estimated by the Chi-square test.The Mann-Whitney U test was performed to compare the serum mi R-4530 levels between the two groups.Area under the receiver operating characteristic(ROC)curves was used to assess the predictive accuracy of mi R-4530.All statistical analyses were performed using SPSS 20.0 software.Results: Of the 74 breast cancer patients,a sensitive group was comprised by 52 patients(70.27%)and a resistant group was comprised by 22 patients(29.73%).The median ages of the two groups were 45 and 49 years old,respectively(range,28–61 years).Regarding the cancer characteristics,a large percentage of patients were diagnosed with T2 tumors,and approximately three-fifths of the patients presented Luminal B subtype.Most of the patients did not achieve p CR,with p CR rates of 16.3% and 9.5% for the sensitive and resistant groups,respectively.Overall,no significant differences were observed between the two groups regarding the clinicopathological characteristics(P > 0.05).In the screening phase,we found 15 significantly upregulated mi RNAs by microarray.Among them,a 2.16-fold change of mi R-4530 was observed between the two groups.And in the validation phase,the levels of serum mi R-4530 were significantly higher in the sensitive group than those in the resistant group(P=0.029).Furthermore,by using mi RNA prediction software,we identified 6,079 target genes of mi R-4530,including runt-related transcription factor 2(RUNX2).It maybe involve in regulation of cell cycle,leading to chemotherapy resistance.Conclusions: In conclusion,our study revealed significant different expression levels of serum mi R-4530 between neoadjuvant chemotherapy-sensitive and resistant patients.Elevated serum mi R-4530 levels may sensitize breast cancer to taxane-and anthracycline-based NAC by suppressing RUNX2.As one of the target genes of serum mi R-4530,RUNX2 may be involved in the process of apoptosis,thus affecting the sensitivity of breast cancer cells to NAC.Therefore,serum mi R-4530 has the potential to be a new biomarker for predicting the sensitivity of neoadjuvant chemotherapy for breast cancer and has certain clinical application prospect. |
PDF Full Text Request