ASSOCIATION OF CACHEXIA AND BODY COMPOSITION WITH CIRCULATING GROWTH DIFFERENTIATION FACTOR-15 (GDF-15) SERUM LEVELS IN PATIENTS WITH GASTRIC AND COLORECTAL CANCER

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy Pub Date : 2026-03-01 Epub Date: 2026-03-05 DOI:10.1016/j.htct.2026.106330

Fabíola Furtuoso Zarpelão, Renata Erbert Contriciani, Larissa Ariel Oliveira, Sandra Regina Branbilla, Leo Victor Kim, Luiz Roberto Lopes, Nelson Adami Andreollo, Maria Emilia Seren Takahashi, Jun Takahashi, Ligia M. Antunes Correa, Celso Dario Ramos, Elba C.S.C. Etchebehere, Maria Carolina Santos Mendes, José Barreto Campello Carvalheira

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引用次数: 0

Abstract

Introduction

Cancer-associated cachexia remains a primary focus of clinical research, with increasing attention on molecular targets such as Growth Differentiation Factor 15 (GDF-15). A recent Phase 2 trial showed that GDF-15 inhibition via ponsegromab improved body weight and physical activity, reinforcing its role as a key driver. While other targets are in development, evidence linking GDF-15 to muscle mass remains inconclusive, and gastric and colorectal cancers are underrepresented in these clinical studies. This landscape underscores the need to investigate the clinical implications of elevated GDF-15 levels across specific oncological populations.

Objective

To investigate associations between body composition, radiodensity, and adipose tissue glucose uptake (via PET/CT) with plasma GDF-15 levels in gastric and colorectal cancer patients.

Methods

This prospective study included patients with gastric/gastroesophageal junction (GEJ) adenocarcinoma (n=67; 42 analyzed for GDF-15) and colorectal cancer (n=46; 38 analyzed for GDF-15). Data were managed via REDCap. Preoperative serum was analyzed for GDF-15 using Luminex®. Body composition was assessed by CT; cachexia followed GLIM (gastric) or Fearon (colorectal) criteria. Statistical analysis in Jamovi 2.3 included Shapiro-Wilk, × 2, Student’s t/Mann-Whitney U, and Spearman’s rank correlation (p<0.05).

Results

In the Gastric/GEJ cohort the median age was 63; 56.7% were male. Mean BMI was 24.5 (±5.05) kg/m²; however, cachexia (35.9%), sarcopenia (40.9%), and myosteatosis (39.4%) were prevalent. Cachectic patients had significantly higher GDF-15 (1028 ± 663 vs. 655 ± 293 pg/mL; p = 0.034). GDF-15 correlated with sarcopenia (rho=0.270, p=0.009), myosteatosis (rho=0.293, p=0.030), and negatively with skeletal muscle attenuation (rho=-0.451, p=0.003). No significant association was found with PET/CT glucose uptake (mean SUV) in visceral adipose tissue (VAT) (p=0.441), subcutaneous adipose tissue (SAT) (p=0.911), or muscle (p=0.072). In the Colorectal cohort the mean age was 62.5; 54.3% male. Mean BMI was 28.6 (± 5.1) kg/m²; cachexia (67.4%), myosteatosis (78.9%), and low muscularity (39.5%) were identified. GDF-15 levels did not differ by cachexia status (p=0.554) but were significantly higher in patients with weight loss (795 ± 400 vs. 404 ± 281pg/mL; p = 0.012). VAT area was significantly larger in patients with GDF-15 >1000 pg/mL (230 ± 35 vs. 136 ± 72, p = 0.017). No association was found with PET/CT uptake in VAT (p=0.774) or SAT (p=0.518).

Conclusion

GDF-15 was associated with cachexia and musculoskeletal impairment in gastric cancer, and with weight loss and visceral adiposity in colorectal cancer. The lack of correlation with PET/CT glucose uptake suggests GDF-15 influences tissue wasting independent of glucose metabolic alterations in these settings. These results highlight GDF-15 as a potential target for personalized therapeutic interventions in gastrointestinal oncology.

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胃癌和结直肠癌患者恶病质和体成分与循环生长分化因子-15 （gdf-15）血清水平的关系

癌症相关恶病质仍然是临床研究的主要焦点，越来越多的关注分子靶点，如生长分化因子15 （GDF-15）。最近的一项2期试验表明，通过ponsegromab抑制GDF-15可以改善体重和身体活动，从而加强了其作为关键驱动因素的作用。虽然其他靶点正在开发中，但将GDF-15与肌肉质量联系起来的证据仍然不确定，而且在这些临床研究中，胃癌和结直肠癌的代表性不足。这种情况强调了研究特定肿瘤人群中GDF-15水平升高的临床意义的必要性。目的探讨胃、结直肠癌患者体成分、放射密度、脂肪组织葡萄糖摄取（PET/CT）与血浆GDF-15水平的关系。方法本前瞻性研究纳入胃/胃食管交界处（GEJ）腺癌患者（n=67， GDF-15分析42例）和结直肠癌患者（n=46， GDF-15分析38例）。数据通过REDCap进行管理。术前血清用Luminex®检测GDF-15。CT评估体成分；恶病质符合GLIM（胃）或Fearon（结肠）标准。Jamovi 2.3的统计分析包括Shapiro-Wilk、 × 2、Student’s t/Mann-Whitney U和Spearman’s秩相关（p<0.05）。结果在胃/GEJ队列中，中位年龄为63岁；56.7%为男性。平均BMI为24.5（±5.05）kg/m²；然而，恶病质（35.9%）、肌肉减少症（40.9%）和肌骨化症（39.4%）普遍存在。恶病质患者GDF-15显著升高（1028±663 vs 655±293 pg/mL; p = 0.034）。GDF-15与肌肉减少症（rho=0.270, p=0.009）、肌骨化症（rho=0.293, p=0.030）相关，与骨骼肌衰减呈负相关（rho=-0.451, p=0.003）。内脏脂肪组织（VAT）（p=0.441）、皮下脂肪组织（SAT）（p=0.911）或肌肉（p=0.072）的PET/CT葡萄糖摄取（平均SUV）未发现显著相关性。结直肠组的平均年龄为62.5岁；54.3%的男性。平均BMI为28.6（±5.1）kg/m²；恶病质（67.4%），骨骼肌病（78.9%）和低肌肉（39.5%）被确定。GDF-15水平没有因恶病质状态而差异（p=0.554），但体重减轻患者的GDF-15水平明显较高（795±400 vs 404±281pg/mL; p = 0.012）。GDF-15 >；1000 pg/mL患者的VAT面积显著增大（230±35 vs 136±72,p = 0.017）。与VAT （p=0.774）或SAT （p=0.518）的PET/CT摄取无关联。结论df -15与胃癌恶病质和肌肉骨骼损伤有关，与结直肠癌体重减轻和内脏肥胖有关。与PET/CT葡萄糖摄取缺乏相关性表明，在这些情况下，GDF-15独立于葡萄糖代谢改变影响组织消耗。这些结果突出了GDF-15作为胃肠道肿瘤个性化治疗干预的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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