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动态变化的不同表型和遗传循环肿瘤细胞作为评估 RCC 预后的生物标志物。

Dynamic changes of different phenotypic and genetic circulating tumor cells as a biomarker for evaluating the prognosis of RCC.

机构信息

a Department of Urology , The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.

出版信息

Cancer Biol Ther. 2019;20(4):505-512. doi: 10.1080/15384047.2018.1537576. Epub 2018 Oct 25.

Abstract

BACKGROUND

Circulating tumor cells (CTCs) and relevant autophagy Beclin-1 genes expression are critical biomarkers for tumorigenesis and tumor progress. Here we investigated the relationship of dynamic changes of CTCs and Beclin-1 expression of CTCs with renal cell carcinoma (RCC) prognosis.

MATERIALS AND METHODS

A total of 69 patients with RCC were enrolled and divided into two groups based on the postoperative status of distant metastasis, including metastasis-free group (n = 58) and metastatic group (n = 11). Demographic characteristics of each patient were recorded in detail. All 69 enrolled patients had received multiple CTC tests and peripheral blood samples were obtained at three different time points (1 day before operation, 6 months and 12 months after operation). Peripheral blood samples were drawn before each time point and CTCs were separated by using Can Patrol CTC enrichment technique. CTCs were divided into epithelial, mesenchymal and mixed phenotype based on different surface biomarkers. RNA in situ hybridization assay was used to detect the expression of Beclin1 gene.

RESULTS

The percentages of epithelial, mesenchymal and mixed CTCs were 11.64%, 28.04% and 60.32%, respectively. There were no significant differences of initial CTCs counts between metastasis-free group (8.43 ± 5.15) and metastatic group (7.71 ± 3.82) (P > 0.05). As for metastatic group, the number of mixed CTCs at 12 months postoperatively was significantly higher than that of mixed CTCs preoperatively and 6 months postoperatively (P < 0.05). In the metastatic group, the number of Beclin1 positive CTCs was significantly higher than that of Beclin1 negative CTCs preoperatively (P < 0.05), moreover, there were several significantly changes of Beclin1 positive CTCs with different types and at different time points.

CONCLUSION

The recurrence or metastasis of RCC was uncorrelated with initial CTCs counts, but probably related with the variation trend of CTCs, especially mesenchymal CTCs and Beclin1 positive CTCs.

摘要

背景

循环肿瘤细胞(CTC)和相关自噬 Beclin-1 基因表达是肿瘤发生和肿瘤进展的关键生物标志物。在这里,我们研究了 CTC 动态变化和 CTCs 中 Beclin-1 表达与肾细胞癌(RCC)预后的关系。

材料和方法

共纳入 69 例 RCC 患者,根据术后远处转移情况分为无转移组(n=58)和转移组(n=11)。详细记录每位患者的人口统计学特征。所有 69 例患者均接受了多次 CTC 检测,并在三个不同时间点(术前 1 天、术后 6 个月和 12 个月)采集外周血样本。在每个时间点之前抽取外周血样本,并使用 Can Patrol CTC 富集技术分离 CTC。根据不同的表面标志物,将 CTC 分为上皮型、间质型和混合表型。采用 RNA 原位杂交法检测 Beclin1 基因的表达。

结果

上皮型、间质型和混合型 CTC 的比例分别为 11.64%、28.04%和 60.32%。无转移组(8.43±5.15)和转移组(7.71±3.82)初始 CTC 计数无显著差异(P>0.05)。对于转移组,术后 12 个月混合 CTC 数量明显高于术前和术后 6 个月(P<0.05)。在转移组中,Beclin1 阳性 CTC 的数量明显高于 Beclin1 阴性 CTC(P<0.05),此外,不同类型和不同时间点的 Beclin1 阳性 CTC 数量均有明显变化。

结论

RCC 的复发或转移与初始 CTC 计数无关,但可能与 CTC 变化趋势有关,尤其是间质型 CTC 和 Beclin1 阳性 CTC。

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