结直肠癌肝转移引发的转移播散：种子会再次离开土壤吗？

Metastatic Spread Emerging From Liver Metastases of Colorectal Cancer: Does the Seed Leave the Soil Again?

作者信息

Rahbari Nuh N, Bork Ulrich, Schölch Sebastian, Reissfelder Christoph, Thorlund Kristian, Betzler Alexander, Kahlert Christoph, Schneider Martin, Ulrich Alexis B, Büchler Markus W, Weitz Jürgen, Koch Moritz

机构信息

*Department of Gastrointestinal, Thoracic and Vascular Surgery, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany †Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada ‡Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.

出版信息

Ann Surg. 2016 Feb;263(2):345-52. doi: 10.1097/SLA.0000000000001341.

DOI:10.1097/SLA.0000000000001341

PMID:26501709

Abstract

OBJECTIVE

To investigate whether liver metastases contribute to metastatic spread of colorectal cancer (CRC) by shedding intact tumor cells.

BACKGROUND

Metastases represent the primary cause of death in CRC. Understanding the metastatic activity of metastases and which patients are at high risk for tumor cell dissemination may, therefore, have significant influence on cancer care in the future.

METHODS

Circulating tumor cells (CTCs) were detected in the hepatic inflow (portal venous blood [PVB]) and outflow compartment (hepatic venous blood [HVB]) of a training (n = 55) and validation (n = 50) set using the CellSearch system. Isolated CTC from the HVB were subjected to gene expression analyses by quantitative polymerase chain reaction.

RESULTS

CTC detection rate (37.2% vs 19.6%; P = 0.04) and count (mean: 12.7, SEM: ± 5.9 vs 1.9; ± 1.2; P = 0.01) were significantly higher in HVB compared to PVB. The increased CTC detection rate (54% vs 11.4%; P < 0.001) and CTC count (14.7 ± 5.1 vs 1.1 ± 0.6; P < 0.001) in the HVB compared to the PVB compartment was confirmed in the validation cohort. Expression of epithelial markers and genes involved in cell-to-cell and cell-to-matrix adhesion was reduced in CTC compared to tumor cells in liver metastases. Metastasis size greater than 5 cm was associated with CTC shedding from established liver metastases in the training and validation cohorts.

CONCLUSIONS

Colorectal liver metastases shed intact tumor cells with an invasive phenotype. Metastasis size serves as a surrogate marker for metastatic activity of colorectal liver metastases.

摘要

目的

研究肝转移灶是否通过脱落完整的肿瘤细胞促进结直肠癌（CRC）的转移扩散。

背景

转移是CRC患者的主要死因。因此，了解转移灶的转移活性以及哪些患者存在肿瘤细胞播散的高风险，可能会对未来的癌症治疗产生重大影响。

方法

使用CellSearch系统在一个训练组（n = 55）和一个验证组（n = 50）的肝流入（门静脉血[PVB]）和流出腔室（肝静脉血[HVB]）中检测循环肿瘤细胞（CTC）。从HVB中分离出的CTC通过定量聚合酶链反应进行基因表达分析。

结果

与PVB相比，HVB中的CTC检测率（37.2%对19.6%；P = 0.04）和计数（平均值：12.7，标准误：±5.9对1.9；±1.2；P = 0.01）显著更高。在验证队列中，与PVB腔室相比，HVB中的CTC检测率（54%对11.4%；P < 0.001）和CTC计数（14.7±5.1对1.1±0.6；P < 0.001）也有所增加。与肝转移灶中的肿瘤细胞相比，CTC中上皮标志物以及参与细胞间和细胞与基质黏附的基因表达降低。在训练组和验证组中，转移灶大小大于5 cm与已形成的肝转移灶中CTC脱落有关。