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

IF 4 3区医学 Q1 OBSTETRICS & GYNECOLOGY Breast Cancer Pub Date : 2024-05-01 Epub Date: 2024-04-01 DOI:10.1007/s12282-024-01553-x

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

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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.

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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

背景：晚期乳腺癌（BC）患者由于复发率和转移率高而预后不佳。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（CTCs）与乳腺癌患者预后之间的关系：本研究共纳入 50 名女性患者。她们的诊断是通过临床特征、图像数据和临床病理确定的。通过CanPatrol™技术和三色原位RNA杂交（RNA-ISH）检测CTC亚型和CTC上TOP2A基因的表达，并根据其表面标记将其分为上皮细胞CTC（eCTC）、间质细胞CTC（MCTC）和混合细胞CTC（HCTC）。治疗前采用免疫组化（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。通过 COX 风险回归模型计算预测复发和转移的风险因素。采用 Kaplan-Meier 生存曲线确定患者的无进展生存期（PFS）：肿瘤体积较大（≥ 3 厘米）和肿瘤结节转移（TNM）分期较晚的患者的总 CTCs（TCTCs）较高（P 结论：肿瘤体积较大（≥ 3 厘米）和肿瘤结节转移（TNM）分期较晚的患者的总 CTCs（TCTCs）较高：高TCTCs、HCTCs和CTCs上TOP2A基因表达阳性是预测BC患者预后的关键生物标志物。BC患者激素受体的阳性表达明显有利于PFS。

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来源期刊

Breast Cancer ONCOLOGY-OBSTETRICS & GYNECOLOGY

CiteScore

6.70

自引率

2.50%

发文量

105

审稿时长

6-12 weeks

期刊介绍： Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.