循环肿瘤细胞中TOP2A基因表达与乳腺癌患者化疗耐药性的相关性研究

The correlation study between TOP2A gene expression in circulating tumor cells and chemotherapeutic drug resistance of patients with breast cancer.

作者信息

Ye Jin-Hui, Yu Jian, Huang Ming-Ying, Mo Yue-Mei

机构信息

Department of Breast Disease, The First People's Hospital of Zhaoqing, Zhaoqing, 526021, Guangdong, China.

出版信息

Breast Cancer. 2024 May;31(3):417-425. doi: 10.1007/s12282-024-01553-x. Epub 2024 Apr 1.

DOI:10.1007/s12282-024-01553-x

PMID:38561479

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11045578/

Abstract

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.

PATIENTS AND 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.

摘要

背景

晚期乳腺癌（BC）患者由于复发和转移率高，预后较差。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。

患者与方法

本研究共纳入50名女性。通过临床特征、影像数据和临床病理确定她们的诊断。采用CanPatrol™技术和三色原位RNA杂交（RNA-ISH）检测CTC亚型及CTC上TOP2A基因的表达，根据表面标志物将其分为上皮性CTC（eCTC）、间充质性CTC（MCTC）和混合性CTC（HCTC）。治疗前采用免疫组织化学（IHC）方法检测激素受体，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。采用COX风险回归模型计算预测复发和转移的危险因素。使用Kaplan-Meier生存曲线确定患者的无进展生存期（PFS）。

结果

肿瘤体积较大（≥3 cm）和肿瘤淋巴结转移（TNM）分期较晚的患者总CTC（TCTC）数量较高（P<0.05）。这些患者的TOP2A表达水平也较高。COX风险回归分析表明，TCTC中的TOP2A表达水平、ER+、HER-2+和TNM分期是患者复发和转移的关键危险因素（P<0.05）。TCTC≥5个、HCTC≥3个且≥3个TCTC中TOP2A表达阳性的患者的PFS显著长于TCTC<5个、HCTC<3个且<3个TCTC中TOP2A表达的患者（P<0.05）。相反，激素受体阳性（ER+、PR+、HER-2+）患者的PFS也明显长于激素受体表达阴性的患者。