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Background <p>Loss of adipose tissue and systemic inflammation are recognized hallmarks of poor prognosis in advanced cancer. However, it is still uncertain whether changes in visceral (VAT) and subcutaneous adipose tissue (SAT) during neoadjuvant chemotherapy (NACT) (beyond static body composition) carry independent prognostic relevance, especially when interpreted alongside the evolving inflammatory response.</p> Methods <p>Between February 2010 and January 2024, patients with LAGC receiving NACT followed by radical gastrectomy were screened across five tertiary centres (n = 587). Visceral and subcutaneous adipose index changes (ΔVAI, ΔSAI) were derived from L3-level computed tomography images, and inflammatory variation was assessed using&#xa0;Δneutrophil-to-lymphocyte ratio (ΔNLR). Transcriptomic profiling of 94 pretreatment tumours explored biological correlates.</p> Results <p>Visceral fat-preserved group conferred a marked survival advantage exclusively in patients with ΔNLR-high(3-year OS: 62.1% vs 32.6%, 3-year RFS: 55.2% vs 22.2%; <i>P</i> &lt; 0.001, respectively). ΔSAI showed modest associations (3-year OS: 63.6% vs 43.7%, <i>P</i> = 0.004; 3-year RFS: 57.5% vs 33.1%, <i>P</i> = 0.001). No survival difference was observed in theΔNLR-low subgroup (<i>P</i> &gt; 0.05). Multivariable analysis confirmed visceral fat-preserved group as an independent protective factor (fully adjusted HR = 0.374, <i>P</i> = 0.001), whereas ΔSAI lost significance after adjustment. The ΔVAI-based prognostic paradigm, derived from findings in the ΔNLR-high subgroup, offered markedly improved risk stratification beyond ypTNM and showed reproducible performance in the validation cohort. Transcriptomic profiling revealed that the high-risk phenotype within the ΔNLR-high subgroup was enriched for EMT activation, angiogenesis, and an M2 macrophage–dominant microenvironment.</p> Conclusion <p>Visceral adipose remodeling is an inflammation-dependent prognostic determinant in LAGC and reflects a biologically aggressive, chemoresistant tumour phenotype.</p> Graphical abstract <p></p>

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When adipose meets inflammation: a novel adiposity–inflammation signature predicts prognosis and chemotherapy benefit in locally advanced gastric cancer

  • 期刊论文

  • 发表日期：

    2026年2月15日

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  • Ling-Kang Zhang,
  • Hua-Long Zheng,
  • Zhi-Long Lin,
  • Xiao-Yun Zheng,
  • Shi-Chao Wu,
  • Guo-Jun Xia,
  • Yong-Hong Wang,
  • Wei-Feng Chen,
  • Qi-Chen He,
  • Jia Lin,
  • Zhi-Wei Zheng,
  • Hong-Hong Zheng,
  • Jian-Xian Lin,
  • Qi-Yue Chen,
  • Ping Li,
  • Chao-Hui Zheng,
  • Chang-Ming Huang,
  • Jian-Wei Xie

摘要

Background

Loss of adipose tissue and systemic inflammation are recognized hallmarks of poor prognosis in advanced cancer. However, it is still uncertain whether changes in visceral (VAT) and subcutaneous adipose tissue (SAT) during neoadjuvant chemotherapy (NACT) (beyond static body composition) carry independent prognostic relevance, especially when interpreted alongside the evolving inflammatory response.

Methods

Between February 2010 and January 2024, patients with LAGC receiving NACT followed by radical gastrectomy were screened across five tertiary centres (n = 587). Visceral and subcutaneous adipose index changes (ΔVAI, ΔSAI) were derived from L3-level computed tomography images, and inflammatory variation was assessed using Δneutrophil-to-lymphocyte ratio (ΔNLR). Transcriptomic profiling of 94 pretreatment tumours explored biological correlates.

Results

Visceral fat-preserved group conferred a marked survival advantage exclusively in patients with ΔNLR-high(3-year OS: 62.1% vs 32.6%, 3-year RFS: 55.2% vs 22.2%; P < 0.001, respectively). ΔSAI showed modest associations (3-year OS: 63.6% vs 43.7%, P = 0.004; 3-year RFS: 57.5% vs 33.1%, P = 0.001). No survival difference was observed in theΔNLR-low subgroup (P > 0.05). Multivariable analysis confirmed visceral fat-preserved group as an independent protective factor (fully adjusted HR = 0.374, P = 0.001), whereas ΔSAI lost significance after adjustment. The ΔVAI-based prognostic paradigm, derived from findings in the ΔNLR-high subgroup, offered markedly improved risk stratification beyond ypTNM and showed reproducible performance in the validation cohort. Transcriptomic profiling revealed that the high-risk phenotype within the ΔNLR-high subgroup was enriched for EMT activation, angiogenesis, and an M2 macrophage–dominant microenvironment.

Conclusion

Visceral adipose remodeling is an inflammation-dependent prognostic determinant in LAGC and reflects a biologically aggressive, chemoresistant tumour phenotype.

Graphical abstract