A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction
Abstract
Background: Cancer-related sarcopenia is associated with poor clinical outcomes but remains difficult to define and quantify in routine oncology practice. Current assessments rely on imaging and functional scales that are time-consuming and provide limited biological insight. We aimed to identify a plasma proteomic signature of cancer-related sarcopenia and to uncover circulating mediators involved in its pathophysiology. Methods: Patients were included from two cohorts of the MATCH-R study (NCT02517892): a discovery cohort of advanced cancer patients treated with immunotherapy and an independent validation cohort of metastatic castration-resistant prostate cancer (mCRPC) patients treated with androgen-receptor pathway inhibitors. External validation was performed in the TRACERx cohort of non-small cell lung cancer. Skeletal muscle index at third lumbar vertebra (L3) was quantified using imaging, and ECOG performance status served as a functional proxy. Plasma proteomics was performed using the Olink Explore platform. An extreme gradient boosting (XGBoost) model was trained on a high-contrast subset using a neuromuscular-focused protein panel and validated across cohorts. Functional effects of candidate mediators were assessed in differentiating human myoblasts. Results: The model generated a continuous sarcopenia probability (SP) score that correlated with muscle mass and functional status and consistently stratified overall survival across cohorts. A reduced four-protein model retained comparable performance, supporting translational applicability. Proteins associated with SP included insulin-like growth factor binding protein 1 and 2 (IGFBP1, IGFBP2), and interleukin-6 (IL6). IGFBP1 and IGFBP2 impaired myoblast differentiation, while IL6 induced IGFBP1 expression in liver cells. Conclusions: Plasma proteomics enables scalable and biologically informed assessment of cancer-related sarcopenia, identifies tumor-host mediators of muscle dysfunction, and supports objective patient stratification for therapeutic intervention.
Related
- Associations of Coexisting Metabolic Dysfunction‐Associated Steatotic Liver Disease and Sarcopenia‐Related Abnormalities With Adverse Clinical Outcomes Across Obesity States
- The Proteomic Profiling of a Platelet-Enriched Fraction Identifies an Inflammatory and Immune-Related Signature Associated with Non-Response to Treatment with Plasma Rich in Growth Factors in Knee Osteoarthritis
- Sarcopenia and Muscle Dysfunction in Older Adults with Burn Injuries: An Integrated Clinical Perspective
- Comprehensive proteomic characterization of the esophageal String Test identifies a luminal protein signature associated with eosinophilic esophagitis.
- Systemic inflammation induces a myocardial inflammatory transcriptional signature without cardiac dysfunction in murine arthritis
BibTeX
@article{dallolio2026plasma,
title = {{A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction}},
author = {Filippo Gustavo Dall’olio and Wael Salem Zrafi and Xinran Song and Littisha Lawrance and Ekaterina Shalimanova and Anna Schwager and Nadia Myszka and Fei Chen and Rebecca Ibrahim and Marie Guinhut and Pierre Busson and Catherine Brenner and Karim Benihoud and Fabrice Barlesi and Caroline Even and Dimitria Brempou and Nathalie Lassau and Claudio Nicotra and Maud Ngo Camus and Marine Aglave and Yohann Loriot and Diana Cardenas and Mariam Jamal-Hanjani and Carla M Prado and Antoine Italiano and Yegor Vassetzky and Benjamin Besse},
journal = {Molecular Cancer},
year = {2026},
month = jun,
doi = {10.1186/s12943-026-02716-4},
url = {https://hal.science/hal-05760261v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction
AU - Filippo Gustavo Dall’olio
AU - Wael Salem Zrafi
AU - Xinran Song
AU - Littisha Lawrance
AU - Ekaterina Shalimanova
AU - Anna Schwager
AU - Nadia Myszka
AU - Fei Chen
AU - Rebecca Ibrahim
AU - Marie Guinhut
AU - Pierre Busson
AU - Catherine Brenner
AU - Karim Benihoud
AU - Fabrice Barlesi
AU - Caroline Even
AU - Dimitria Brempou
AU - Nathalie Lassau
AU - Claudio Nicotra
AU - Maud Ngo Camus
AU - Marine Aglave
AU - Yohann Loriot
AU - Diana Cardenas
AU - Mariam Jamal-Hanjani
AU - Carla M Prado
AU - Antoine Italiano
AU - Yegor Vassetzky
AU - Benjamin Besse
PY - 2026
DA - 2026/06/29
JO - Molecular Cancer
DO - 10.1186/s12943-026-02716-4
UR - https://hal.science/hal-05760261v1
AB - Background: Cancer-related sarcopenia is associated with poor clinical outcomes but remains difficult to define and quantify in routine oncology practice. Current assessments rely on imaging and functional scales that are time-consuming and provide limited biological insight. We aimed to identify a plasma proteomic signature of cancer-related sarcopenia and to uncover circulating mediators involved in its pathophysiology. Methods: Patients were included from two cohorts of the MATCH-R study (NCT02517892): a discovery cohort of advanced cancer patients treated with immunotherapy and an independent validation cohort of metastatic castration-resistant prostate cancer (mCRPC) patients treated with androgen-receptor pathway inhibitors. External validation was performed in the TRACERx cohort of non-small cell lung cancer. Skeletal muscle index at third lumbar vertebra (L3) was quantified using imaging, and ECOG performance status served as a functional proxy. Plasma proteomics was performed using the Olink Explore platform. An extreme gradient boosting (XGBoost) model was trained on a high-contrast subset using a neuromuscular-focused protein panel and validated across cohorts. Functional effects of candidate mediators were assessed in differentiating human myoblasts. Results: The model generated a continuous sarcopenia probability (SP) score that correlated with muscle mass and functional status and consistently stratified overall survival across cohorts. A reduced four-protein model retained comparable performance, supporting translational applicability. Proteins associated with SP included insulin-like growth factor binding protein 1 and 2 (IGFBP1, IGFBP2), and interleukin-6 (IL6). IGFBP1 and IGFBP2 impaired myoblast differentiation, while IL6 induced IGFBP1 expression in liver cells. Conclusions: Plasma proteomics enables scalable and biologically informed assessment of cancer-related sarcopenia, identifies tumor-host mediators of muscle dysfunction, and supports objective patient stratification for therapeutic intervention.
SN - 1476-4598
ER -