背景:晚期乳腺癌(BC)患者由于高复发率和转移率而预后不良。预测预后的生物标志物仍有待探索。本研究旨在评估循环肿瘤细胞(CTC)与BC患者预后之间的关系。
方法:本研究共纳入50名女性。他们的诊断是由临床特征决定的,图像数据,和临床病理学。通过CanPatrol™技术和三色原位RNA杂交(RNA-ISH)检测CTC亚型和TOP2A基因在CTC上的表达,分为上皮CTC(eCTC),间充质CTC(MCTC),和基于其表面标记的杂合CTC(HCTC)。激素受体,包括雌激素受体(ER),孕激素受体(PR),和人表皮生长因子受体2(HER-2)的表达,治疗前通过免疫组织化学(IHC)方法测量。采用COX风险回归模型计算预测复发转移的危险因素。使用Kaplan-Meier生存曲线确定患者的无进展生存期(PFS)。
结果:肿瘤大小较大(≥3cm)且肿瘤淋巴结转移(TNM)分期晚期的患者总CTC(TCTC)较高(P<0.05)。这些患者还具有高的TOP2A表达水平。COX风险回归分析表明TCTCs中TOP2A的表达水平,ER+,HER-2+,TNM分期是患者复发转移的危险因素(P<0.05)。≥5个TCTC患者的PFS,≥3个HCTC,≥3个TCTC的TOP2A阳性表达明显长于<5个TCTC的患者,<3个HCTC,TCTCs中TOP2A表达<3(P<0.05)。相比之下,激素受体阳性患者的PFS(ER+,PR+,HER-2)的寿命也比激素受体表达阴性的患者明显更长。
结论:高TCTC,HCTCs,CTC上TOP2A基因表达阳性是预测BC患者预后的关键生物标志物。激素受体阳性表达在BC患者中具有显著偏向性PFS。
BACKGROUND: Patients with breast cancer (BC) at advanced stages have poor outcomes because of high rate of recurrence and metastasis. Biomarkers for predicting prognosis remain to be explored. This
study aimed to evaluate the relationships between circulating tumor cells (CTCs) and outcomes of BC patients.
METHODS: A total of 50 female were enrolled in this
study. Their diagnoses were determined by clinical characteristics, image data, and clinical pathology. CTC subtypes and TOP2A gene expression on CTCs were detected by CanPatrol™ technology and triple color in situ RNA hybridization (RNA-ISH), which divided into epithelial CTCs (eCTCs), mesenchymal CTCs (MCTCs), and hybrid CTCs (HCTCs) based on their surface markers. Hormone receptor, including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, was measured by immunohistochemistry (IHC) method before treatment. The risk factors for predicting recurrence and metastasis were calculated by COX risk regression model. The progression-free survival (PFS) of patients was determined using Kaplan-Meier survival curve.
RESULTS: The patients with a large tumor size (≥ 3 cm) and advanced tumor node metastasis (TNM) stages had high total CTCs (TCTCs) (P < 0.05). These patients also had high TOP2A expression level. COX risk regression analysis indicated that TOP2A expression levels in TCTCs, ER + , HER-2 + , and TNM stages were critical risk factors for recurrence and metastasis of patients (P < 0.05). The PFS of patients with ≥ 5 TCTCs, ≥ 3 HCTCs, and positive TOP2A expression in ≥ 3 TCTCs was significantly longer than that in patient with < 5 TCTCs, < 3 HCTCs, and TOP2A expression in < 3 TCTCs (P < 0.05). In contrast, the PFS of patients with positive hormone receptors (ER + , PR + , HER-2 +) also was dramatically lived longer than that in patients with negative hormone receptor expression.
CONCLUSIONS: High TCTC, HCTCs, and positive TOP2A gene expression on CTCs were critical biomarkers for predicting outcomes of BC patients. Positive hormone receptor expression in BC patients has significant favor PFS.