Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月29日

查看全文
  • Filippo Gustavo Dall’Olio,
  • Wael Salem Zrafi,
  • Xinran Song,
  • Littisha Lawrance,
  • Ekaterina Shalimanova,
  • Anna Schwager,
  • Nadia Myszka,
  • Fei Chen,
  • Rebecca Ibrahim,
  • Marie Guinhut,
  • Pierre Busson,
  • Catherine Brenner,
  • Karim Benihoud,
  • Fabrice Barlesi,
  • Caroline Even,
  • Dimitria Brempou,
  • Nathalie Lassau,
  • Claudio Nicotra,
  • Maud Ngo Camus,
  • Marine Aglave,
  • Yohann Loriot,
  • Diana Cardenas,
  • Mariam Jamal-Hanjani,
  • Carla M Prado,
  • Antoine Italiano,
  • Yegor Vassetzky,
  • Benjamin Besse

摘要

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.

Graphical Abstract