乳腺癌化疗患者并发肺部感染血清微小RNA表达谱

Serum microRNA expression profile in breast cancer patients with pulmonary infection during chemotherapy

目的研究乳腺癌患者化疗期间并发肺部感染血清微小RNA(miRNA)表达谱差异。方法选取2018年1月-2020年4月在南阳医学高等专科学校第一附属医院放疗科接受化疗且化疗期间发生肺部感染的乳腺癌患者102例,纳入肺部感染组,另随机选取49例同期在医院接受化疗期间且未发生感染性疾病,年龄与肺部感染组相匹配的乳腺癌患者纳入未感染组;应用Solexa平台测序分析两组血清miRNA表达谱变化,实时荧光定量PCR(qRT-PCR)法验证血清特异性miRNA;绘制受试者工作特征(ROC)曲线分析血清特异性miRNA对乳腺癌患者化疗期间并发肺部感染的预测价值。结果较未感染组,肺部感染组有19个miRNA表达上调,24个miRNA表达下调,其中表达倍数上调或下调2倍以上miRNA 7个,分别为has-miR-18b-3p、has-miR-146a、has-miR-155、has-miR-125b、has-miR-3195、has-miR-53、has-miR-16-5p;qRT-PCR法结果与高通量测序结果一致,高通量测序结果有效;7个差异化表达miRNA中,miR-18b-3p预测乳腺癌化疗期间肺部感染的曲线下面积值(AUC)最高,以2.351为miR-18b-3p相对表达量cut-off,其预测乳腺癌化疗期间肺部感染的敏感度、特异度分别为92.16%、100.00%。结论乳腺癌患者化疗期间,并发肺部感染患者与未感染患者的血清miRNA表达谱存在特异性变化,其中特异性miR-18b-3p可作为此类患者化疗期间肺部感染的风险预测因子。

OBJECTIVE To study the serum microRNA(miRNA)expression profile in breast cancer patients with pulmonary infection during chemotherapy.METHODS Between Jan 2018 and Apr 2020,102 breast cancer patients who received chemotherapy and developed pulmonary infection during chemotherapy were enrolled in the pulmonary infection group.Meanwhile,49 patients who received chemotherapy during the same period and did not have infectious diseases were included in the uninfected group.Solexa platform sequencing was performed to analyze the differences in serum miRNA expression profiles between the two groups,and the qRT-PCR method was used to determine serum specific miRNAs.The receiver operating characteristic(ROC)curves were used to analyze the predictive value of serum-specific miRNA for pulmonary infection in breast cancer patients during chemotherapy.RESULTS In the pulmonary infection group,the expression of 19 miRNAs was up-regulated,24 miRNAs were down-regulated,and the expression of 7 miRNAs were up-regulated or down-regulated at two fold,which were has-miR-18 b-3 p,has-miR-146 a,has-miR-155,has-miR-125 b,has-miR-3195,has-miR-53,and has-miR-16-5 p.The qRT-PCR results were consistent with high-throughput sequencing results,which showed the high-throughput sequencing results were valid.Among the 7 differentially expressed miRNAs,the area under the curve(AUC)value of miR-18 b-3 p for predicting pulmonary infection during breast cancer chemotherapy was the largest.When the cut-off value of relative expression level of miR-18 b-3 p was 2.351,the sensitivity and specificity in predicting pulmonary infection during breast cancer chemotherapy were 92.16%and 100.00%.CONCLUSION During chemotherapy,there are specific changes in serum miRNA expression profiles between patients with lung infection and those without,and specific miR-18 b-3 p can be used as a risk predictor of pulmonary infection in such patients.