Todorović-Raković Nataša, Milovanović Jelena, Greenman John, Radulovic Marko
Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
Adv Med Sci. 2021 Sep;66(2):359-365. doi: 10.1016/j.advms.2021.07.007. Epub 2021 Jul 22.
Improved prognostication of a patient's outcome could allow for personalized treatment decisions in breast cancer. Homeobox B7 (HOXB7) and interleukin 17 receptor B (IL17RB) are proteins reportedly involved in the development of hormonal therapy resistance. Their prognostic value was previously investigated in tumor tissue but recent mass spectrometric detection of HOXB7 and IL17RB proteins in serum has prompted us to perform the first prognostic evaluation of their serum levels.
The study included 81 premenopausal breast cancer patients that received adjuvant hormonal therapy. The median follow-up period was 61 months. HOXB7 and IL17RB serum protein levels were measured by quantitative sandwich ELISA and prognostically evaluated by Cox proportional hazards regression analysis.
HOXB7 protein was detected in 96.3% and IL17RB in 33.3% of serum samples. Higher levels of serum HOXB7 significantly associated with favorable disease outcome by prognosticating distant (by HR = 0.04; P = 0.001) and local recurrence (by HR = 0.03, P = 0.001). The recurrence rates in the HOXB7 and HOXB7 subgroups of patients (cut-off 81.5 pg/mL) were 0% and 17%, respectively. Serum IL17RB levels did not significantly associate with either local or distant events. The multivariate analysis highlighted estrogen receptor, histological grade, nodal status and HOXB7 as independent prognostic parameters.
Our findings validate the previous mass-spectrometry data by showing that HOXB7 and IL17RB cellular proteins are detectable in serum by a standard ELISA assay. Furthermore, we show that HOXB7 serum levels are the relevant prognosticator of response to hormonal therapy.
改善对患者预后的预测有助于乳腺癌的个性化治疗决策。据报道，同源盒B7（HOXB7）和白细胞介素17受体B（IL17RB）蛋白参与激素治疗耐药的发生发展。此前已对它们在肿瘤组织中的预后价值进行了研究，但最近血清中HOXB7和IL17RB蛋白的质谱检测促使我们首次对其血清水平进行预后评估。
本研究纳入了81例接受辅助激素治疗的绝经前乳腺癌患者。中位随访期为61个月。通过定量夹心酶联免疫吸附测定法检测血清中HOXB7和IL17RB蛋白水平，并通过Cox比例风险回归分析进行预后评估。
96.3%的血清样本中检测到HOXB7蛋白，33.3%的血清样本中检测到IL17RB蛋白。血清HOXB7水平较高与远处复发（风险比[HR]=0.04；P=0.001）和局部复发（HR=0.03，P=0.001）的良好疾病预后显著相关。HOXB7水平高于81.5 pg/mL的患者亚组和低于该水平的患者亚组的复发率分别为0%和17%。血清IL17RB水平与局部或远处事件均无显著相关性。多变量分析突出了雌激素受体、组织学分级、淋巴结状态和HOXB7作为独立的预后参数。
我们的研究结果通过标准酶联免疫吸附测定法在血清中检测到HOXB7和IL17RB细胞蛋白，验证了之前的质谱数据。此外，我们表明血清HOXB7水平是激素治疗反应的相关预后指标。
