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通过基于大小的平台检测到的循环肿瘤微栓子(CTM)和波形蛋白阳性循环肿瘤细胞(CTC)可预测晚期结直肠癌患者化疗期间的预后较差。

Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy.

作者信息

Zhang Dejun, Zhao Lei, Zhou Pengfei, Ma Hong, Huang Fang, Jin Min, Dai Xiaomeng, Zheng Xiumei, Huang Shaoyi, Zhang Tao

机构信息

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 Hubei People's Republic of China.

Wuhan YZY Medical Science & Technology Co., Ltd., Wuhan, 430075 Hubei People's Republic of China.

出版信息

Cancer Cell Int. 2017 Jan 5;17:6. doi: 10.1186/s12935-016-0373-7. eCollection 2017.

Abstract

BACKGROUND

Circulating tumor cells (CTCs) detected in peripheral blood (PB) of cancer patients can be identified as isolated CTCs and circulating tumor microemboli (CTM). This study aimed to evaluate the prognostic value of CTM detection and CTC phenotype in advanced colorectal cancer (CRC) patients during chemotherapy.

METHODS

A size-based platform for CTC isolation was applied. PB samples (5 ml) from 98 advanced CRC patients during 2-6 cycles chemotherapy were collected for CTC detection, and CTC count was correlated to patient's clinicopathological characteristics and clinical outcome. And CTC phenotype was measured by immunofluorescent staining and evaluate the predictive significance on survival in 32 CTCs-positive patients with advanced CRC.

RESULTS

Forty-eight of 98 patients were CTCs-positive, including 18 CTM-positive patients, and CTC detection was positively correlated with lymphatic invasion ( = 0.049), TNM stage ( = 0.023), and serum CEA level ( = 0.014). Moreover, Kaplan-Meier survival and Cox regression analyses revealed that the presence of CTCs was an independent factor for poor PFS and OS ( < 0.05) in advanced CRC patients during chemotherapy, and CTM-positive patients had shooter survival than isolated CTCs-positive patients ( < 0.05). Furthermore, patients with vimentin+ isolated CTCs/CTM had shorter PFS and OS compared with CK+ CTCs ( < 0.05).

CONCLUSIONS

This study provided evidence that the presence of CTCs was positively correlated with poor prognosis, and furthermore, CTM and vimentin+ CTCs predicted poorer survival, which indicated that CTM and vimentin+ CTCs detected by a sensitive platform could be used to improve prognostic value of CTCs in advanced CRC patients under treatment.

摘要

背景

在癌症患者外周血(PB)中检测到的循环肿瘤细胞(CTC)可分为孤立性CTC和循环肿瘤微栓子(CTM)。本研究旨在评估CTM检测及CTC表型对晚期结直肠癌(CRC)患者化疗期间的预后价值。

方法

应用基于大小的CTC分离平台。收集98例晚期CRC患者在2 - 6个化疗周期的PB样本(5 ml)用于CTC检测,并将CTC计数与患者的临床病理特征及临床结局相关联。通过免疫荧光染色检测CTC表型,并评估其对32例晚期CRC CTC阳性患者生存的预测意义。

结果

98例患者中有48例CTC阳性,其中18例CTM阳性,CTC检测与淋巴侵犯(P = 0.049)、TNM分期(P = 0.023)及血清CEA水平(P = 0.014)呈正相关。此外,Kaplan - Meier生存分析和Cox回归分析显示,化疗期间晚期CRC患者中CTC的存在是无进展生存期(PFS)和总生存期(OS)差的独立因素(P < 0.05),CTM阳性患者的生存期短于孤立性CTC阳性患者(P < 0.05)。此外,波形蛋白阳性的孤立性CTC/CTM患者与细胞角蛋白(CK)阳性的CTC患者相比,PFS和OS更短(P < 0.05)。

结论

本研究表明,CTC的存在与不良预后呈正相关,此外,CTM和波形蛋白阳性的CTC预示着更差的生存,这表明通过敏感平台检测到的CTM和波形蛋白阳性的CTC可用于提高晚期CRC患者治疗中CTC的预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e8d/5217234/ef0190558c8e/12935_2016_373_Fig1_HTML.jpg

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