瘤内微生物组促进胃肠道间质瘤的肝转移并抑制伊马替尼的辅助治疗。
Intratumoral microbiome promotes liver metastasis and dampens adjuvant imatinib treatment in gastrointestinal stromal tumor.
发表日期：2024 Aug 06
作者：
Yanze Li, Ruizhi Zhang, Chengbo Fu, Qi Jiang, Peng Zhang, Yong Zhang, Jingchao Chen, Kaixiong Tao, Wei-Hua Chen, Xiangyu Zeng
来源：
CANCER LETTERS
摘要：
了解胃肠道间质瘤 (GIST) 患者长期肝转移 (LM) 结局的决定因素至关重要。我们在手术中建立了瘤内微生物组的特征选择模型，在发现组 (n = 74) 和验证组 (n = 34) 中分别实现了 0.953 和 0.897 AUC 的稳健预测精度。值得注意的是，尽管伊马替尼 (AI) 辅助治疗显着减少了 LM 的发生，但瘤内微生物组对术后 LM 产生了独立更强的影响。采用 16S 和全长 rRNA 测序，我们确定细胞内希瓦氏藻是接受 AI 和未接受 AI 治疗的患者中最重要的 LM 危险因素。实验验证证实了 S. algae 在 GIST 中的瘤内存在，以及对 GIST 细胞的迁移/侵袭促进作用。此外，S. algae 在转移性小鼠模型中促进 LM 并阻碍 AI 治疗。我们的研究结果主张在手术中纳入瘤内微生物组评估，并建议将 S. algae 作为 GIST LM 抑制的治疗靶点。版权所有 © 2024。由 Elsevier B.V 出版。
Understanding the determinants of long-term liver metastasis (LM) outcomes in gastrointestinal stromal tumor (GIST) patients is crucial. We established the feature selection model of intratumoral microbiome at the surgery, achieving robust predictive accuracies of 0.953 and 0.897 AUCs in discovery (n = 74) and validation (n = 34) cohorts, respectively. Notably, despite the significant reduction in LM occurrence with adjuvant imatinib (AI) treatment, intratumoral microbiome exerted independently stronger effects on post-operative LM. Employing both 16S and full-length rRNA sequencing, we pinpoint intracellular Shewanella algae as a foremost LM risk factor in both AI- and non-AI-treated patients. Experimental validation confirmed S. algae's intratumoral presence in GIST, along with migration/invasion-promoting effects on GIST cells. Furthermore, S. algae promoted LM and impeded AI treatment in metastatic mouse models. Our findings advocate for incorporating intratumoral microbiome evaluation at surgery, and propose S. algae as a therapeutic target for LM suppression in GIST.Copyright © 2024. Published by Elsevier B.V.