TY - JOUR
T1 - High-density single cell mRNA sequencing to characterize circulating tumor cells in hepatocellular carcinoma
AU - D’Avola, Delia
AU - Villacorta-Martin, Carlos
AU - Martins-Filho, Sebastiao N.
AU - Craig, Amanda
AU - Labgaa, Ismail
AU - von Felden, Johann
AU - Kimaada, Allette
AU - Bonaccorso, Antoinette
AU - Tabrizian, Parissa
AU - Hartmann, Boris M.
AU - Sebra, Robert
AU - Schwartz, Myron
AU - Villanueva, Augusto
N1 - Funding Information:
A.V. is the recipient of the American Association for the Study of Liver Diseases Foundation (AASLDF) Alan Hofmann Clinical and Translational Research Award, and he is supported by the U.S. Department of Defense (CA150272P3) and the Tisch Cancer Institute (Cancer Center Grant P30 CA196521). A.J.C. is supported by the National Cancer Institute Ruth L. Kirschstein NRSA Institutional Research Training Grant (CA078207). I.L. is supported by a grant from the Swiss National Science Foundation, from Foundation Roberto & Gianna Gonella and Foundation SICPA. D.D. is supported by the Grant for Studies Broadening from the Spanish Association for the Study of the Liver (Asociación Española para el Estudio del Hígado, AEEH) and the Cancer Research Grant from NuovoSoldati Foundation. J.v.F. is supported by Deutsche Forschungsgemeinschaft (German Research Foundation). B.M.H. is supported by PRIME (Program for Research on Immune Modeling and Experimentation), an NIAID-funded Modeling Immunity for Biodefense Center (Grant U19 AI117873). The authors thank the office of Scientific Computing and the Genomics Core Facility at the Icahn School of Medicine at Mount Sinai (ISMMS) for providing computational resources and staff expertise, the Flow Cytometry Core at the ISMMS and Yolanda Garcia (Department of Immunology, ISMMS) for technical support.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Patients with hepatocellular carcinoma (HCC) release tumor cells to the bloodstream, which can be detected using cell surface markers. Despite numerous reports suggest a direct correlation between the number of circulating tumor cells (CTCs) and poor clinical outcomes, few studies have provided a thorough molecular characterization of CTCs. Due to the limited access to tissue samples in patients at advanced stages of HCC, it is crucial to develop new technologies to identify HCC cancer drivers in routine clinical conditions. Here, we describe a method that sequentially combines image flow cytometry and high density single-cell mRNA sequencing to identify CTCs in HCC patients. Genome wide expression profiling of CTCs using this approach demonstrates CTC heterogeneity and helps detect known oncogenic drivers in HCC such as IGF2. This integrated approach provides a novel tool for biomarker development in HCC using liquid biopsy.
AB - Patients with hepatocellular carcinoma (HCC) release tumor cells to the bloodstream, which can be detected using cell surface markers. Despite numerous reports suggest a direct correlation between the number of circulating tumor cells (CTCs) and poor clinical outcomes, few studies have provided a thorough molecular characterization of CTCs. Due to the limited access to tissue samples in patients at advanced stages of HCC, it is crucial to develop new technologies to identify HCC cancer drivers in routine clinical conditions. Here, we describe a method that sequentially combines image flow cytometry and high density single-cell mRNA sequencing to identify CTCs in HCC patients. Genome wide expression profiling of CTCs using this approach demonstrates CTC heterogeneity and helps detect known oncogenic drivers in HCC such as IGF2. This integrated approach provides a novel tool for biomarker development in HCC using liquid biopsy.
UR - http://www.scopus.com/inward/record.url?scp=85050985488&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-30047-y
DO - 10.1038/s41598-018-30047-y
M3 - Article
C2 - 30068984
AN - SCOPUS:85050985488
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11570
ER -