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Background <p>Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related deaths by 2040, with the highest disease burden expected amongst Non-Hispanic Black patients. One of the most significant predictors of poor outcomes is the presence of cancer-associated cachexia (CCa). Yet, race- and ethnicity-specific biomarkers for early CCa diagnosis are lacking.</p> Methods <p>We evaluated a panel of candidate biomarkers of CCa in a diverse cohort of patients with pre-treatment serum using multiplex ELISA-based methods.</p> Results <p>We find that growth/differentiation factor-15 (GDF-15) is associated with cachexia severity, is superior to standard biomarkers at classifying cachexia, and differentiates between non-cachexia and pre-cachexia status, but only among Hispanic/Latinx and non-Hispanic White participants. Furthermore, high GDF-15 levels at diagnosis are associated with a greater weight loss from 3.3% (95%CI = −0.14–6.7) to 8.0% (CI = 5.9–10.1) over the 6 months post-diagnosis. Finally, both ENA-78/CXCL5 and GRO-α/CXCL1 are elevated in non-Hispanic Black individuals in a disease-independent manner (P &lt; 0.001 for both analytes).</p> Conclusions <p>GDF-15 may be a potential biomarker for “pre-cachexia” in the non-Hispanic White and the Hispanic population, but not non-Hispanic Black individuals. These findings underscore the unmet need to enroll non-Hispanic Black participants in clinical trials for CCa.</p>

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Race-based differences in serum biomarkers for cancer-associated cachexia in a diverse cohort of patients with pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月18日

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  • Margaret A. Park,
  • Evan W. Davis,
  • Solomon Alhassan,
  • J. Pablo Arnoletti,
  • Toni L. Basinski,
  • Ashley B. McKee,
  • Mark Bloomston,
  • Tiffany L. Carson,
  • Tiago Biachi de Castria,
  • Dung-Tsa Chen,
  • Elena M. Cortizas,
  • Sylvia L. Crowder,
  • Maria Genilo Delgado,
  • Wade G. Douglas,
  • Jason B. Fleming,
  • Pamela Hodul,
  • Kevin L. Huguet,
  • Kun Jiang,
  • Dae Won Kim,
  • John Koomen,
  • Anjuli K. Luthra,
  • Mokenge Malafa,
  • Anjana A. Menon,
  • Raiza Morales,
  • Nipun B. Merchant,
  • Kenneth Meredith,
  • Qianxing Mo,
  • Manual A. Molina-Vega,
  • Lina Moreno-Urazan,
  • Kayode D. Olumoyin,
  • Nathan Parker,
  • Jose M. Pimiento,
  • Ghulam Rasool,
  • Katarzyna A. Rejniak,
  • Samer Sansil,
  • Lauren M. Sparks,
  • Paul Stewart,
  • Alexandra F. Tassielli,
  • Jamie K. Teer,
  • Dan Viet Tran,
  • Jose G. Trevino,
  • Vic Velanovich,
  • Christopher J. Whelan,
  • Daniel Jeong,
  • Sarah M. Judge,
  • Andrew R. Judge,
  • Jennifer B. Permuth

摘要

Background

Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related deaths by 2040, with the highest disease burden expected amongst Non-Hispanic Black patients. One of the most significant predictors of poor outcomes is the presence of cancer-associated cachexia (CCa). Yet, race- and ethnicity-specific biomarkers for early CCa diagnosis are lacking.

Methods

We evaluated a panel of candidate biomarkers of CCa in a diverse cohort of patients with pre-treatment serum using multiplex ELISA-based methods.

Results

We find that growth/differentiation factor-15 (GDF-15) is associated with cachexia severity, is superior to standard biomarkers at classifying cachexia, and differentiates between non-cachexia and pre-cachexia status, but only among Hispanic/Latinx and non-Hispanic White participants. Furthermore, high GDF-15 levels at diagnosis are associated with a greater weight loss from 3.3% (95%CI = −0.14–6.7) to 8.0% (CI = 5.9–10.1) over the 6 months post-diagnosis. Finally, both ENA-78/CXCL5 and GRO-α/CXCL1 are elevated in non-Hispanic Black individuals in a disease-independent manner (P < 0.001 for both analytes).

Conclusions

GDF-15 may be a potential biomarker for “pre-cachexia” in the non-Hispanic White and the Hispanic population, but not non-Hispanic Black individuals. These findings underscore the unmet need to enroll non-Hispanic Black participants in clinical trials for CCa.