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Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients

Overview of attention for article published in BMC Cancer, September 2016
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  • Good Attention Score compared to outputs of the same age (65th percentile)
  • Good Attention Score compared to outputs of the same age and source (77th percentile)

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Title
Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients
Published in
BMC Cancer, September 2016
DOI 10.1186/s12885-016-2758-3
Pubmed ID
Authors

Archana Anantharaman, Terence Friedlander, David Lu, Rachel Krupa, Gayatri Premasekharan, Jeffrey Hough, Matthew Edwards, Rosa Paz, Karla Lindquist, Ryon Graf, Adam Jendrisak, Jessica Louw, Lyndsey Dugan, Sarah Baird, Yipeng Wang, Ryan Dittamore, Pamela L. Paris

Abstract

While programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity in a proportion of patients with advanced bladder cancer, strongly predictive and prognostic biomarkers are still lacking. In this study, we evaluated PD-L1 protein expression on circulating tumor cells (CTCs) isolated from patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer and explore the prognostic value of CTC PD-L1 expression on clinical outcomes. Blood samples from 25 patients with MIBC or mBCa were collected at UCSF and shipped to Epic Sciences. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC identification by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK)(+) and (CK)(-)CTCs (CD45(-), intact nuclei, morphologically distinct from WBCs) were enumerated. A subset of patient samples underwent genetic characterization by fluorescence in situ hybridization (FISH) and copy number variation (CNV) analysis. CTCs were detected in 20/25 (80 %) patients, inclusive of CK(+) CTCs (13/25, 52 %), CK(-)CTCs (14/25, 56 %), CK(+) CTC Clusters (6/25, 24 %), and apoptotic CTCs (13/25, 52 %). Seven of 25 (28 %) patients had PD-L1(+) CTCs; 4 of these patients had exclusively CK(-)/CD45(-)/PD-L1(+) CTCs. A subset of CTCs were secondarily confirmed as bladder cancer via FISH and CNV analysis, which revealed marked genomic instability. Although this study was not powered to evaluate survival, exploratory analyses demonstrated that patients with high PD-L1(+)/CD45(-)CTC burden and low burden of apoptotic CTCs had worse overall survival. CTCs are detectable in both MIBC and mBCa patients. PD-L1 expression is demonstrated in both CK(+) and CK(-)CTCs in patients with mBCa, and genomic analysis of these cells supports their tumor origin. Here we demonstrate the ability to identify CTCs in patients with advanced bladder cancer through a minimally invasive process. This may have the potential to guide checkpoint inhibitor immune therapies that have been established to have activity, often with durable responses, in a proportion of these patients.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 98 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 1%
Unknown 97 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 22 22%
Student > Ph. D. Student 19 19%
Other 11 11%
Student > Bachelor 10 10%
Student > Postgraduate 5 5%
Other 12 12%
Unknown 19 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 27 28%
Medicine and Dentistry 21 21%
Agricultural and Biological Sciences 9 9%
Engineering 4 4%
Chemistry 4 4%
Other 8 8%
Unknown 25 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 September 2016.
All research outputs
#7,408,406
of 23,577,654 outputs
Outputs from BMC Cancer
#1,991
of 8,530 outputs
Outputs of similar age
#110,363
of 322,912 outputs
Outputs of similar age from BMC Cancer
#40
of 174 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 8,530 research outputs from this source. They receive a mean Attention Score of 4.4. This one has done well, scoring higher than 76% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 322,912 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 174 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.