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Clinical utility of the S3-score for molecular prediction of outcome in non-metastatic and metastatic clear cell renal cell carcinoma

Overview of attention for article published in BMC Medicine, July 2018
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Title
Clinical utility of the S3-score for molecular prediction of outcome in non-metastatic and metastatic clear cell renal cell carcinoma
Published in
BMC Medicine, July 2018
DOI 10.1186/s12916-018-1088-5
Pubmed ID
Authors

Florian Büttner, Stefan Winter, Steffen Rausch, Jörg Hennenlotter, Stephan Kruck, Arnulf Stenzl, Marcus Scharpf, Falko Fend, Abbas Agaimy, Arndt Hartmann, Jens Bedke, Matthias Schwab, Elke Schaeffeler

Abstract

Stratification of cancer patients to identify those with worse prognosis is increasingly important. Through in silico analyses, we recently developed a gene expression-based prognostic score (S3-score) for clear cell renal cell carcinoma (ccRCC), using the cell type-specific expression of 97 genes within the human nephron. Herein, we verified the score using whole-transcriptome data of independent cohorts and extend its application for patients with metastatic disease receiving tyrosine kinase inhibitor treatment. Finally, we sought to improve the signature for clinical application using qRT-PCR. A 97 gene-based S3-score (S397) was evaluated in a set of 52 primary non-metastatic and metastatic ccRCC patients as well as in 53 primary metastatic tumors of sunitinib-treated patients. Gene expression data of The Cancer Genome Atlas (n = 463) was used for platform transfer and development of a simplified qRT-PCR-based 15-gene S3-score (S315). This S315-score was validated in 108 metastatic and non-metastatic ccRCC patients and ccRCC-derived metastases including in part several regions from one metastasis. Univariate and multivariate Cox regression stratified by T, N, M, and G were performed with cancer-specific and progression-free survival as primary endpoints. The S397-score was significantly associated with cancer-specific survival (CSS) in 52 ccRCC patients (HR 2.9, 95% Cl 1.0-8.0, PLog-rank = 3.3 × 10-2) as well as progression-free survival in sunitinib-treated patients (2.1, 1.1-4.2, PLog-rank = 2.2 × 10-2). The qRT-PCR based S315-score performed similarly to the S397-score, and was significantly associated with CSS in our extended cohort of 108 patients (5.0, 2.1-11.7, PLog-rank = 5.1 × 10-5) including metastatic (9.3, 1.8-50.0, PLog-rank = 2.3 × 10-3) and non-metastatic patients (4.4, 1.2-16.3, PLog-rank = 1.6 × 10-2), even in multivariate Cox regression, including clinicopathological parameters (7.3, 2.5-21.5, PWald = 3.3 × 10-4). Matched primary tumors and metastases revealed similar S315-scores, thus allowing prediction of outcome from metastatic tissue. The molecular-based qRT-PCR S315-score significantly improved prediction of CSS by the established clinicopathological-based SSIGN score (P = 1.6 × 10-3). The S3-score offers a new clinical avenue for ccRCC risk stratification in the non-metastatic, metastatic, and sunitinib-treated setting.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 9 100%

Demographic breakdown

Readers by professional status Count As %
Professor 2 22%
Student > Master 2 22%
Researcher 1 11%
Student > Ph. D. Student 1 11%
Unknown 3 33%
Readers by discipline Count As %
Medicine and Dentistry 4 44%
Nursing and Health Professions 1 11%
Biochemistry, Genetics and Molecular Biology 1 11%
Unknown 3 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 06 July 2018.
All research outputs
#13,245,850
of 16,669,654 outputs
Outputs from BMC Medicine
#2,487
of 2,637 outputs
Outputs of similar age
#209,183
of 280,312 outputs
Outputs of similar age from BMC Medicine
#1
of 1 outputs
Altmetric has tracked 16,669,654 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,637 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.1. This one is in the 2nd percentile – i.e., 2% of its peers scored the same or lower than it.
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 280,312 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
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