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A Comprehensive Molecular Analysis of in Vivo Isolated EpCAM-Positive Circulating Tumor Cells in Breast Cancer
Clinical Chemistry ( IF 7.1 ) Pub Date : 2021-06-24 , DOI: 10.1093/clinchem/hvab099
Areti Strati 1 , Martha Zavridou 1 , Galatea Kallergi 2, 3 , Eleni Politaki 2 , Andra Kuske 4 , Tobias M Gorges 4 , Sabine Riethdorf 4 , Simon A Joosse 4 , Claudia Koch 4 , Anna-Lena Bohnen 5 , Volkmar Mueller 5 , George Koutsodontis 6 , Emmanouil Kontopodis 7 , Nikiforita Poulakaki 8 , Amanda Psyrri 6 , Dimitris Mavroudis 2, 7 , Vasilis Georgoulias 2 , Klaus Pantel 4 , Evi S Lianidou 1
Affiliation  

Background Circulating tumor cell (CTC) analysis is highly promising for liquid biopsy-based molecular diagnostics. We undertook a comprehensive molecular analysis of in vivo isolated CTCs in breast cancer (BrCa). Methods In vivo isolated CTCs from 42 patients with early and 23 patients with metastatic breast cancer (MBC) were prospectively collected and analyzed for gene expression, DNA mutations, and DNA methylation before and after treatment. 19 healthy donor (HD) samples were analyzed as a control group. In identical blood draws, CTCs were enumerated using CellSearch® and characterized by direct IF staining. Results All 19 HD samples were negative for CK8, CK18, CK19, ERBB2, TWIST1, VEGF, ESR1, PR, and EGFR expression, while CD44, CD24, ALDH1, VIM, and CDH2 expression was normalized to B2M (reference gene). At least one gene was expressed in 23/42 (54.8%) and 8/13 (61.5%) CTCs in early BrCa before and after therapy, and in 20/23 (87.0%) and 5/7 (71.4%) MBC before and after the first cycle of therapy. PIK3CA mutations were detected in 11/42 (26.2%) and 3/13 (23.1%) in vivo isolated CTCs in early BrCa before and after therapy, and in 11/23 (47.8%) and 2/7 (28.6%) MBC, respectively. ESR1 methylation was detected in 5/32 (15.7%) and 1/10 (10.0%) CTCs in early BrCa before and after therapy, and in 3/15(20.0%) MBC before the first line of therapy. The comprehensive molecular analysis of CTC revealed a higher sensitivity in relation to CellSearch or IF staining when based on creatine kinase selection. Conclusions In vivo-CTC isolation in combination with a comprehensive molecular analysis at the gene expression, DNA mutation, and DNA methylation level comprises a highly powerful approach for molecular diagnostic applications using CTCs.

中文翻译:

乳腺癌体内分离的 EpCAM 阳性循环肿瘤细胞的综合分子分析

背景 循环肿瘤细胞 (CTC) 分析对于基于液体活检的分子诊断非常有前景。我们对乳腺癌 (BrCa) 中体内分离的 CTC 进行了全面的分子分析。方法前瞻性收集 42 例早期患者和 23 例转移性乳腺癌 (MBC) 患者体内分离的 CTC,并分析治疗前后的基因表达、DNA 突变和 DNA 甲基化。19 个健康供体 (HD) 样本作为对照组进行分析。在相同的抽血中,使用 CellSearch® 计数 CTC,并通过直接 IF 染色进行表征。结果所有19例HD样本CK8、CK18、CK19、ERBB2、TWIST1、VEGF、ESR1、PR和EGFR表达均为阴性,而CD44、CD24、ALDH1、VIM和CDH2表达均归一化为B2M(参考基因)。至少一个基因在 23/42 (54.8%) 和 8/13 (61.5%) 的 CTC 中表达于早期 BrCa 治疗前后,以及在 20/23 (87.0%) 和 5/7 (71.4%) 的 MBC 之前并且在第一个治疗周期之后。PIK3CA 突变在 11/42 (26.2%) 和 3/13 (23.1%) 在治疗前后早期 BrCa 体内分离的 CTC 中检测到,在 11/23 (47.8%) 和 2/7 (28.6%) MBC 中检测到, 分别。在治疗前后早期 BrCa 的 5/32 (15.7%) 和 1/10 (10.0%) CTC 中检测到 ESR1 甲基化,在一线治疗前在 3/15 (20.0%) MBC 中检测到 ESR1 甲基化。当基于肌酸激酶选择时,CTC 的综合分子分析揭示了与 CellSearch 或 IF 染色相关的更高灵敏度。结论 体内-CTC 分离结合基因表达、DNA 突变、
更新日期:2021-06-24
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