Neoadjuvant Treatment Based on Gastric Cancer Molecular Subtyping: Chemotherapy, Immunotherapy, or Targeted Therapy?-A Retrospective Analysis.

IF 3.5 2区医学 Q2 ONCOLOGY

Annals of Surgical Oncology Pub Date : 2025-10-01 Epub Date: 2025-07-03 DOI:10.1245/s10434-025-17738-3

Hua-Long Zheng, Li-Li Shen, Qiao-Ling Zheng, Jian-Xian Lin, Chang-Ming Huang, Zheng-Deng Lei, Chao-Hui Zheng

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引用次数: 0

Abstract

Background: This study aimed to identify the most effective drug therapeutics for patients with the mesenchymal subtype of advanced gastric cancer (AGC). Extensive research employing diverse omics methodologies has unveiled a varied landscape of AGC. Recent progress in next-generation sequencing and other genomic technologies has facilitated a more intricate exploration of AGC at the molecular level. Nonetheless, the optimal treatment for patients with the mesenchymal subtype of gastric cancer remains elusive. Lei's molecular classification of AGC is based on gene expression profiles named "mesenchymal," "immunogenic," "classical," and "metabolic."

Patients and methods: Based on RNA-seq transcriptome, 234 patients were divided into four molecular subtypes: mesenchymal (n = 96), immunogenic (n = 37), metabolic (n = 61), and classic (n = 40).

Results: Among those with mesenchymal-subtype AGC, compared with non-Apatinib group, the Apatinib treatment group demonstrated a significant increase in objective response rate (ORR 89.3% versus 69.3%, p = 0.038; odds ratio (OR) 0.269, 95% confidence interval (CI) (0.073-0.989)); overall survival (OS) 89.3% versus 60.2%, p = 0.010; hazard ratio (HR) 0.241, 95% CI (0.073-0.796)) and disease-free survival (DFS 78.6% versus 52.9%, p = 0.031; HR 0.400, 95% CI (0.167-0.956)). Furthermore, Apatinib significantly reduced the risk of death and recurrence in patients with mesenchymal subtype (OS: HR 0.129, 95% CI (0.030-0.563), p = 0.006; DFS: HR 0.340, 95% CI (0.138-0.833), p = 0.018). However, no significant differences were observed in the ORR, OS, or DFS between patients with metabolic and classical subtypes who underwent combination chemotherapy with additional Apatinib or camrelizumab.

Conclusions: Our analysis has revealed that, for neoadjuvant therapy in AGC, the mesenchymal subtype stands out as the ideal patient population benefiting from Apatinib.

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基于胃癌分子分型的新辅助治疗：化疗、免疫治疗还是靶向治疗？-回顾性分析。

背景：本研究旨在确定晚期胃癌（AGC）间充质亚型患者最有效的药物治疗方法。采用不同组学方法的广泛研究揭示了AGC的不同景观。新一代测序和其他基因组技术的最新进展促进了在分子水平上对AGC进行更复杂的探索。尽管如此，对于胃癌间充质亚型患者的最佳治疗方法仍然难以捉摸。Lei的AGC分子分类是基于被命名为“间充质”、“免疫原性”、“经典”和“代谢”的基因表达谱。患者和方法：基于RNA-seq转录组，234例患者分为4个分子亚型：间充质（n = 96）、免疫原性（n = 37）、代谢性（n = 61）和典型（n = 40）。结果：间充质亚型AGC患者中，与非阿帕替尼组相比，阿帕替尼治疗组客观有效率显著提高(ORR 89.3% vs 69.3%, p = 0.038；优势比（OR） 0.269, 95%可信区间（CI）（0.073 ~ 0.989）；总生存率（OS） 89.3% vs 60.2%, p = 0.010；风险比（HR） 0.241, 95% CI(0.073-0.796))和无病生存率(DFS 78.6% vs 52.9%, p = 0.031；Hr 0.400, 95% ci(0.167-0.956))。此外，阿帕替尼显著降低间充质亚型患者的死亡和复发风险(OS: HR 0.129, 95% CI (0.030-0.563), p = 0.006；DFS: HR 0.340, 95% CI (0.138 ~ 0.833), p = 0.018)。然而，代谢亚型和经典亚型患者在接受额外的阿帕替尼或camrelizumab联合化疗后的ORR、OS或DFS没有显著差异。结论：我们的分析显示，对于AGC的新辅助治疗，间充质亚型作为受益于阿帕替尼的理想患者群体脱颖而出。

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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来源期刊

Annals of Surgical Oncology 医学-外科

CiteScore

5.90

自引率

10.80%

发文量

1698

审稿时长

2.8 months

期刊介绍： The Annals of Surgical Oncology is the official journal of The Society of Surgical Oncology and is published for the Society by Springer. The Annals publishes original and educational manuscripts about oncology for surgeons from all specialities in academic and community settings.