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Open Access 01-12-2018 | Research article

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

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

Published in: BMC Medicine | Issue 1/2018

Abstract

Background

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.

Methods

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.

Results

The S3₉₇-score was significantly associated with cancer-specific survival (CSS) in 52 ccRCC patients (HR 2.9, 95% Cl 1.0–8.0, P_Log-rank = 3.3 × 10^–2) as well as progression-free survival in sunitinib-treated patients (2.1, 1.1–4.2, P_Log-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, P_Log-rank = 5.1 × 10^–5) including metastatic (9.3, 1.8–50.0, P_Log-rank = 2.3 × 10^–3) and non-metastatic patients (4.4, 1.2–16.3, P_Log-rank = 1.6 × 10^–2), even in multivariate Cox regression, including clinicopathological parameters (7.3, 2.5–21.5, P_Wald = 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).

Conclusion

The S3-score offers a new clinical avenue for ccRCC risk stratification in the non-metastatic, metastatic, and sunitinib-treated setting.

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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
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
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2018
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-018-1088-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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