ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Schlafen 11 (SLFN11) as a prognostic and potentially predictive biomarker in soft tissue sarcoma: evidence from a real-world cohort
Adrian Georg Simon
Su Ir Lyu
David Stahl
Lars Mortimer Schiffmann
Birte Wenk
Reinhard Büttner
Nora Würdemann
Armin Tuchscherer
Roland Tillmann Ullrich
Alexander Quaas
University Hospital of Cologne, Cologne, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract
Background: Soft tissue sarcomas (STS) carry a high risk of relapse or metastasis even after complete resection. (Neo-)adjuvant chemotherapy benefits only a subset of patients, underscoring the need for predictive biomarkers. Schlafen 11 (SLFN11) has emerged as a marker of sensitivity to DNA-damaging agents. This study evaluated SLFN11 as a prognostic and predictive biomarker for (neo-)adjuvant chemotherapy in STS. Materials and Methods: SLFN11 expression was assessed by immunohistochemistry in 242 patients with STS across different disease stages, using the H-score and percentage of positive tumor cells. Sub-cohorts included patients receiving neoadjuvant therapy (n = 33), primary resection (n = 193), palliative first-line chemotherapy (n = 26), or a palliative salvage therapy with trabectedin (n = 22). Associations between SLFN11 levels, clinicopathological features, and survival were analyzed. Results: In the neoadjuvant cohort, SLFN11 expression correlated with pathological tumor regression after chemotherapy alone (rho = 0.73, p = 0.016) and chemotherapy ± radiotherapy (rho = 0.62, p = 0.011). Among primarily resected STS treated with adjuvant chemotherapy ± radiotherapy, SLFN11-high tumors were associated with significantly longer overall survival (OS) (p = 0.007) and disease-free survival (DFS) (p = 0.022). SLFN11 was independently associated with improved outcome (OS: HR 0.06, p = 0.002; DFS: HR 0.08, p = 0.004). In the palliative first-line chemotherapy cohort, SLFN11-high tumors showed improved OS (p = 0.005) and progression-free survival (PFS) (p = 0.024), and SLFN11 remained independently predictive (OS: HR 0.11, p = 0.001). In the trabectedin cohort, SLFN11-high tumors demonstrated longer OS (p = 0.04) and PFS (p = 0.024). Conclusion: SLFN11 is a prognostic and potentially predictive biomarker in STS in the context of chemotherapy. Our results support a prospective validation, standardization of SLFN11 assessment, and consecutive clinical implementation.
Summary
Keywords
DNA-damaging agents, precision medicine, predictive biomarker, prognostic biomarker, schlafen 11, SLFN11, Soft Tissue Sarcoma, Trabectedin
Received
20 January 2026
Accepted
20 February 2026
Copyright
© 2026 Simon, Lyu, Stahl, Schiffmann, Wenk, Büttner, Würdemann, Tuchscherer, Ullrich and Quaas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Adrian Georg Simon
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.