mRNA-Seq of Single Prostate Cancer Circulating Tumor Cells Reveals Recapitulation of Gene Expression and Pathways Found in Prostate Cancer

Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors and enumeration of CTCs is currently used as a prognostic indicator of survival in metastatic prostate cancer patients. Some evidence suggests that it is possible to derive additional information about tumors from expressio...

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Bibliographic Details
Published in:PloS one Vol. 7; no. 11; p. e49144
Main Authors: Cann, Gordon M., Gulzar, Zulfiqar G., Cooper, Samantha, Li, Robin, Luo, Shujun, Tat, Mai, Stuart, Sarah, Schroth, Gary, Srinivas, Sandhya, Ronaghi, Mostafa, Brooks, James D., Talasaz, AmirAli H.
Format: Journal Article
Language:English
Published: United States Public Library of Science 07.11.2012
Public Library of Science (PLoS)
Subjects:
Analysis
Apoptosis
Biology
Biomarkers, Tumor - blood
Blood
Cancer
Cancer genetics
Cancer metastasis
Cell Line, Tumor
Engineering
Enumeration
Gene expression
Gene Expression Regulation, Neoplastic
Human subjects
Humans
Kinases
Leukocytes
Male
Medicine
Messenger RNA
Metabolic Networks and Pathways
Metastases
Metastasis
Neoplasm Metastasis - genetics
Neoplasm Metastasis - pathology
Neoplastic Cells, Circulating - metabolism
Neoplastic Cells, Circulating - pathology
Patients
Prognosis
Prostate cancer
Prostatic Neoplasms - blood
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Ribonucleic acid
RNA
RNA, Messenger - blood
RNA, Messenger - genetics
Sequence Alignment
Sequence Analysis, RNA
Solid tumors
Transcription
Transcription (Genetics)
Tumor cells
Tumors
Urology
United States > US
California
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors and enumeration of CTCs is currently used as a prognostic indicator of survival in metastatic prostate cancer patients. Some evidence suggests that it is possible to derive additional information about tumors from expression analysis of CTCs, but the technical difficulty of isolating and analyzing individual CTCs has limited progress in this area. To assess the ability of a new generation of MagSweeper to isolate intact CTCs for downstream analysis, we performed mRNA-Seq on single CTCs isolated from the blood of patients with metastatic prostate cancer and on single prostate cancer cell line LNCaP cells spiked into the blood of healthy donors. We found that the MagSweeper effectively isolated CTCs with a capture efficiency that matched the CellSearch platform. However, unlike CellSearch, the MagSweeper facilitates isolation of individual live CTCs without contaminating leukocytes. Importantly, mRNA-Seq analysis showed that the MagSweeper isolation process did not have a discernible impact on the transcriptional profile of single LNCaPs isolated from spiked human blood, suggesting that any perturbations caused by the MagSweeper process on the transcriptional signature of isolated cells are modest. Although the RNA from patient CTCs showed signs of significant degradation, consistent with reports of short half-lives and apoptosis amongst CTCs, transcriptional signatures of prostate tissue and of cancer were readily detectable with single CTC mRNA-Seq. These results demonstrate that the MagSweeper provides access to intact CTCs and that these CTCs can potentially supply clinically relevant information.
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Conceived and designed the experiments: AT JDB GMC ZGG. Performed the experiments: GMC ZGG RL SL MT SS. Analyzed the data: SC AT GMC ZGG MR JDB. Contributed reagents/materials/analysis tools: GS SS JDB AT. Wrote the paper: GMC AT ZGG JDB.
Competing Interests: The authors have read the journal's policy and have the following conflicts: GMC, SC, RL, SL, MT, SS, GS, MR, and AT are currently employed by Illumina. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0049144