Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients

BMC Cancer

Research Article

Reinhard Horvat¹  Michael B Fischer²  Jalid Sehouli³  Michael Krainer⁴  Dan Tong⁵  Muy-Kheng M Tea⁵  Christian F Singer⁵  Alexander Reinthaller⁵  Eva Obermayr⁶  Robert Zeillinger⁶  Fatima Sanchez-Cabo⁷  Georg Heinze⁸ 

[1] Clinical Institute of Pathology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria;Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - University Medicine of Berlin, Berlin, Germany;Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;Ludwig Boltzmann Gesellschaft - Cluster Translational Oncology, A-1090, Vienna, Austria;Institute for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria;Section of Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;

关键词: Ovarian Cancer;    Breast Cancer Patient;    Endometrial Cancer;    Circulate Tumor Cell;    Ovarian Cancer Patient;   

DOI  :  10.1186/1471-2407-10-666

 received in 2010-02-22, accepted in 2010-12-03,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe presence of circulating tumor cells (CTC) in the peripheral blood of cancer patients has been described for various solid tumors and their clinical relevance has been shown. CTC detection based on the analysis of epithelial antigens might be hampered by the genetic heterogeneity of the primary tumor and loss of epithelial antigens. Therefore, we aimed to identify new gene markers for the PCR-based detection of CTC in female cancer patients.MethodsGene expression of 38 cancer cell lines (breast, ovarian, cervical and endometrial) and of 10 peripheral blood mononuclear cell (PBMC) samples from healthy female donors was measured using microarray technology (Applied Biosystems). Differentially expressed genes were identified using the maxT test and the 50% one-sided trimmed maxT-test. Confirmatory RT-qPCR was performed for 380 gene targets using the AB TaqMan® Low Density Arrays. Then, 93 gene targets were analyzed using the same RT-qPCR platform in tumor tissues of 126 patients with primary breast, ovarian or endometrial cancer. Finally, blood samples from 26 healthy women and from 125 patients (primary breast, ovarian, cervical, or endometrial cancer, and advanced breast cancer) were analyzed following OncoQuick enrichment and RNA pre-amplification. Likewise, hMAM and EpCAM gene expression was analyzed in the blood of breast and ovarian cancer patients. For each gene, a cut-off threshold value was set at three standard deviations from the mean expression level of the healthy controls to identify potential markers for CTC detection.ResultsSix genes were over-expressed in blood samples from 81% of patients with advanced and 29% of patients with primary breast cancer. EpCAM gene expression was detected in 19% and 5% of patients, respectively, whereas hMAM gene expression was observed in the advanced group (39%) only. Multimarker analysis using the new six gene panel positively identified 44% of the cervical, 64% of the endometrial and 19% of the ovarian cancer patients.ConclusionsThe panel of six genes was found superior to EpCAM and hMAM for the detection of circulating tumor cells in the blood of breast cancer, and they may serve as potential markers for CTC derived from endometrial, cervical, and ovarian cancers.

【 授权许可】

CC BY   
© Obermayr et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.