An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma.

Autor:	Kalinich M; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Bhan I; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Kwan TT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Miyamoto DT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Javaid S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., LiCausi JA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Milner JD; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Hong X; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Goyal L; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Sil S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Choz M; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Ho U; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129., Kapur R; Center for Bioengineering in Medicine, Massachusetts General Hospital and Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114., Muzikansky A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Zhang H; Department of Physics, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138., Weitz DA; Department of Physics, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138., Sequist LV; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Ryan DP; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Chung RT; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Zhu AX; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Isselbacher KJ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu kisselbacher@mgh.harvard.edu.; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Ting DT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.; Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Toner M; Center for Bioengineering in Medicine, Massachusetts General Hospital and Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114.; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Maheswaran S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu kisselbacher@mgh.harvard.edu.; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114., Haber DA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu kisselbacher@mgh.harvard.edu.; Division of Hematology Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.; Howard Hughes Medical Institute, Chevy Chase, MD 20815.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Jan 31; Vol. 114 (5), pp. 1123-1128. Date of Electronic Publication: 2017 Jan 17.
DOI:	10.1073/pnas.1617032114
Abstrakt:	Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and enriches for CTCs with well-preserved RNA. Application of RNA-based digital PCR to detect CTC-derived signatures may thus enable highly accurate tissue lineage-based cancer detection in blood specimens. As proof of principle, we examined hepatocellular carcinoma (HCC), a cancer that is derived from liver cells bearing a unique gene expression profile. After identifying a digital signature of 10 liver-specific transcripts, we used a cross-validated logistic regression model to identify the presence of HCC-derived CTCs in nine of 16 (56%) untreated patients with HCC versus one of 31 (3%) patients with nonmalignant liver disease at risk for developing HCC (P < 0.0001). Positive CTC scores declined in treated patients: Nine of 32 (28%) patients receiving therapy and only one of 15 (7%) patients who had undergone curative-intent ablation, surgery, or liver transplantation were positive. RNA-based digital CTC scoring was not correlated with the standard HCC serum protein marker alpha fetoprotein (P = 0.57). Modeling the sequential use of these two orthogonal markers for liver cancer screening in patients with high-risk cirrhosis generates positive and negative predictive values of 80% and 86%, respectively. Thus, digital RNA quantitation constitutes a sensitive and specific CTC readout, enabling high-throughput clinical applications, such as noninvasive screening for HCC in populations where viral hepatitis and cirrhosis are prevalent. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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