Evidence map›Paper›PMID 28096363›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

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

Mark Kalinich, Irun Bhan, Tanya T Kwan, David T Miyamoto, Sarah Javaid, Joseph A LiCausi, John D Milner, Xin Hong, Lipika Goyal, Srinjoy Sil and 15 more

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.

  1. Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2020
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  8. Review: Detection of Cancer Biomarkers from a Clinical Perspective.International journal of molecular sciences · 2025
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38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 3 institutions in 1 country.

Mark KalinichMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Irun BhanMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Tanya T KwanMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
David T MiyamotoMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Sarah JavaidMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Joseph A LiCausiMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
John D MilnerMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Xin HongMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Lipika GoyalMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Srinjoy SilMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Melissa ChozMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Uyen HoMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Ravi KapurCenter for Bioengineering in Medicine, Massachusetts General Hospital and Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114.
Alona MuzikanskyMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Huidan ZhangDepartment of Physics, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
David A WeitzDepartment of Physics, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Lecia V SequistMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
David P RyanMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Raymond T ChungDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
Andrew X ZhuMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Kurt J IsselbacherMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu kisselbacher@mgh.harvard.edu.
David T TingMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129.
Mehmet TonerCenter for Bioengineering in Medicine, Massachusetts General Hospital and Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114.
Shyamala MaheswaranMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu kisselbacher@mgh.harvard.edu.
Daniel A HaberMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129; dhaber@mgh.harvard.edu maheswaran@helix.mgh.harvard.edu kisselbacher@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USHoward Hughes Medical Institute · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Point-of care Microfluidics for Early Detection of CancerU01EB012493 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., TONER, MEHMET · 2010 to 2018
$19.6M
RESEARCH TRAINING IN DIGESTIVE DISEASES AND NUTRITIONT32DK007191 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1986 to 2026
$14.6M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Tumor Cell Biology Training ProgramT32CA009361 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, NATHANAEL SCHIANDER · 1985 to 2015
$8.9M
Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor CellsR01CA129933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber · 2008 to 2026
$7.5M
Patient-Oriented Research on Hepatitis in Special PopulationsK24DK078772 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T · 2007 to 2016
$1.6M
BIOLOGY OF THE OVARIAN FOLLICLE STEM CELLSF32CA009361 · NCI · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · PI MARGOLIS, JONATHAN S · 1992 to 1994
–
Howard Hughes Medical InstituteNCI NIH HHS F32 CA009361NCI NIH HHS R01 CA129933NCI NIH HHS T32 CA009361NIBIB NIH HHS U01 EB012493NIDDK NIH HHS K24 DK078772NIDDK NIH HHS T32 DK007191NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

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.

Indexed as

High-Throughput Screening AssaysNeoplastic Cells, CirculatingTranscriptomeBiomarkers, TumorCarcinoma, HepatocellularCell LineageCell SeparationEarly Detection of CancerHepatitis B, ChronicHep G2 CellsHigh-Throughput Nucleotide SequencingHumansLab-On-A-Chip DevicesLiver CirrhosisLiver NeoplasmsLogistic ModelsBiomarkers, TumorRNA, MessengerRNA, Neoplasmblood biopsycirculating tumor cellsearly cancer detectionhepatocellular carcinomapredictive modeling

Identifiers

PMID28096363
PMCPMC5293050
OpenAlexW2572403213

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.