KRT19 和 CEACAM5 mRNA 标记的循环肿瘤细胞预示乳腺癌患者的不良预后。

KRT19 and CEACAM5 mRNA-marked circulated tumor cells indicate unfavorable prognosis of breast cancer patients.

机构信息

First Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, 1 Huan-Hu Xi Road, Ti-Yuan Bei, He Xi, Tianjin, 300060, People's Republic of China.

Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.

出版信息

Breast Cancer Res Treat. 2019 Apr;174(2):375-385. doi: 10.1007/s10549-018-05069-9. Epub 2018 Dec 8.

DOI:10.1007/s10549-018-05069-9

PMID:30535933

Abstract

AIM

To investigate the clinical and prognostic significance of circulated tumor cells (CTC) marked by cytokeratin 19 coding gene KRT19 mRNA and carcinoembryonic antigen coding gene CEACAM5 mRNA in preoperative peripheral blood of breast cancer patients and provide molecular markers for breast cancer metastasis risk.

METHODS

The mRNA levels of KRT19 and CEACAM5 in preoperative peripheral blood of breast cancer patients without (n = 603) and with (n = 76) distant metastases at the time of initial diagnosis were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between CTC, CTC and clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), or overall survival (OS) was statistically analyzed.

RESULTS

In different pathological stages of breast cancer, the rates of CTC and CTC increased with the increase of the stages (P = 0.077 and P = 0.004). Preoperative CTC in breast cancer patients was closely related to the lymph node metastasis statues (P < 0.0001), and had no significant correlation with other clinicopathological features. There was no significant correlation between CTC and the clinicopathological features. Patients with high levels of CTC double-marked by KRT19 and CEACAM5 mRNA had shorter DMFS (P < 0.0001) and OS (P = 0.016) for patients with breast cancer. The 7-year DMFS rates for the low-, intermediate-, and high-risk groups were 90.7%, 67.5%, and 59.1%, respectively (P < 0.0001). The prognosis of patients with decreased KRT19 and CEACAM5 mRNA after treatment is better than that of patients who have not decreased, and the combination of the two indicators is better than the single one for predicting PFS (P = 0.002 compare with P = 0.036 or P = 0.047).

CONCLUSION

Double-marked CTC by KRT19 and CEACAM5 mRNA is a prognostic index of breast cancer patients before surgery and after chemotherapy. Single-marked CTC by KRT19 mRNA indicates lymph node statues of preoperative patients. Therefore, the RT-qPCR-based molecular diagnosis of CTC could be used for prognostic prediction of breast cancer patients and guiding clinical treatment.

摘要

目的

研究术前外周血中细胞角蛋白 19 编码基因 KRT19mRNA 和癌胚抗原编码基因 CEACAM5mRNA 标记的循环肿瘤细胞（CTC）在乳腺癌患者中的临床和预后意义，为乳腺癌转移风险提供分子标志物。

方法

采用逆转录定量聚合酶链反应（RT-qPCR）检测术前无（n=603）和有（n=76）远处转移的乳腺癌患者外周血中 KRT19 和 CEACAM5mRNA 的水平。统计分析 CTC、CTC 与临床病理特征、局部无复发生存（LRFS）、远处无转移生存（DMFS）或总生存（OS）的关系。

结果

在不同病理阶段的乳腺癌中，CTC 和 CTC 的检出率随阶段的升高而升高（P=0.077 和 P=0.004）。术前乳腺癌患者 CTC 与淋巴结转移状态密切相关（P<0.0001），与其他临床病理特征无显著相关性。CTC 与临床病理特征无显著相关性。KRT19 和 CEACAM5mRNA 双标记的 CTC 水平高的乳腺癌患者 DMFS（P<0.0001）和 OS（P=0.016）较短。低、中、高危组的 7 年 DMFS 率分别为 90.7%、67.5%和 59.1%（P<0.0001）。治疗后 KRT19 和 CEACAM5mRNA 降低患者的预后优于未降低患者，且两指标联合预测 PFS 优于单一指标（P=0.002 与 P=0.036 或 P=0.047）。