热休克蛋白-90α在乳腺癌诊断和疗效监测及复发预测中的临床价值

Clinical value of heat shock protein-90α on diagnosis, prediction of treatment response,and monitoring of relapse in breast cancer

目的:探讨乳腺癌及其他恶性肿瘤患者血浆中的热休克蛋白-90α(heat shock protein-90α,HSP-90α)表达水平差异,及在乳腺癌诊断、监测疗效、预测复发中的临床价值。方法:选取2016年6月至2016年9月就诊于中国医学科学院肿瘤医院615例女性患者的临床病理资料,分为试验组399例和对照组216例。试验组均为乳腺癌患者,再分为静态组289例和动态组110例,静态组根据TNM分期、组织学类型和分子分型等进行分类分析,动态组用于动态疗效分析;对照组包括健康对照人群103例,乳腺良性肿瘤患者51例及非乳腺系统恶性肿瘤患者62例。采用酶联免疫法检测HSP-90α表达水平。利用ROC曲线分析确定血浆中HSP-90α表达水平作为乳腺癌诊断、复发的截断值,采用Wilcoxon符号秩检验及Kruskal-Wallis检验分析各因素与HSP-90α表达水平的相关性。结果:乳腺癌患者血浆中的HSP-90α表达水平显著升高(P<0.001),且乳腺癌不同分子亚型患者血浆中的HSP-90α表达水平无显著性差异(P>0.05)。选取HSP-90α表达水平为59.7 ng/m L与43.22 ng/m L作为诊断乳腺癌和预测肿瘤复发的临界值时,其曲线下面积(area under curve,AUC)分别为0.834与0.877,灵敏度和特异度分别为90.3%和78.6%与95.7%和74.5%。新辅助治疗有效者及手术前后患者血浆中的HSP-90α表达水平明显下降(P<0.05),结论:乳腺癌患者血浆中的HSP-90α表达水平显著升高,对乳腺癌诊断、疗效判断及复发预测具有一定的价值。

Objective: To explore the prognostic value of heat shock protein-90α(HSP-90α) plasma levels on breast cancer and nonbreast malignant tumors, monitoring the response of chemotherapy, and the predictive value of cancer recurrence and metastasis.Methods: A total of 615 female patients were enrolled between June 2016 and September 2016 in Cancer Hospital, Chinese Academy of Medical Sciences, who were divided into the examination(n=389) and control(n=216) groups. The former group consisted of static(n=289) and dynamic(n=110) groups, which were analyzed by stages, histological and molecular type, and so on. The latter group included healthy people(n=103), and those with breast benign tumors(n=51) and non-breast malignant tumors(n=62). In all the plasma samples, HSP-90α was detected using a double-antibody enzyme-linked immunosorbent assay. The receiving-operating characteristic curve was used to analyze the effectiveness of plasma HSP-90α in the diagnosis of breast cancer. Wilcoxon’s rank test and the KruskalWallis test were used to analyze the association between clinical characteristics and levels of plasma HSP-90α. Results: The levels of plasma HSP-90α were significantly higher in patients with breast cancer than in healthy controls(P<0.001). When the cut-off value was set as 59.7 ng/mL for the diagnosis of breast cancer and 43.22 ng/mL for disease recurrence, the areas under the curve were 0.834 and 0.877, sensitivities were 90.3% and 95.7%, and specificities were 78.6% and 74.5%, respectively. The levels of plasma HSP-90α significantly decreased after achieving a response to neoadjuvant chemotherapy or surgery(P<0.05). Conclusions: Plasma HSP-90α has good clinical value in the diagnosis and monitoring of response and recurrence in breast cancer.