Intratumoral Fusobacterium Nucleatum Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma
Intratumoral Fusobacterium Nucleatum Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma
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DOI：
10.1158/1078-0432.ccr-19-0318
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发表时间：
2019-10-15
影响因子：
11.5
通讯作者：
Goel, Ajay
中科院分区：
文献类型：
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作者：
Yamamura, Kensuke;Izumi, Daisuke;Goel, Ajay
目的：越来越多的证据表明，肠道微生物群在肿瘤发病机制中起着至关重要的作用。虽然核梭杆菌与多种癌症的预后不良有关，但它在预测食道鳞癌患者化疗疗效方面的临床意义尚不清楚。实验设计：采用定量聚合酶链式反应方法定量检测来自两个独立队列的551例食管鳞癌患者肿瘤组织中核梭杆菌的水平，其中包括101例在根治性切除前接受新辅助化疗的患者。使用实体肿瘤反应评估标准(RECISTS)、正电子发射计算机断层扫描(PET/CT)最大标准摄取值(SUVmax)变化定义的原发肿瘤代谢反应(SUVmax)和病理肿瘤消退分级(TRG)来评估核杆菌负荷与无复发生存率(RF)以及化疗疗效的关系。P=0.004)。重要的是，高水平的食管鳞癌患者在RECIST(P=0.04)、PET/CT的SUVmax改变(P=0.0004)和TRG(P=0.003)这三种评估方法上均显示出较差的化疗疗效。更重要的是，我们的数据表明，较高的核杆菌负担与对新辅助化疗的不良反应有关，这表明针对这种细菌的抗生素干预可能会显著改善ESCC患者的治疗反应。
Purpose: Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although Fusobacterium nucleatum (F. nucleatum) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear.Experimental Design: The F. nucleatum levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between F. nucleatum burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation criteria in solid tumors (RECISTs), primary tumor metabolic response defined by maximum standardized uptake value (SUVmax) changes in positron emission tomography-CT (PET/CT), and pathologic tumor regression grade (TRG).Results: High burden of F. nucleatum in patients with ESCC associated with poor RFS in both training [log-rank P = 0.02; HR = 1.61; P = 0.03] and validation cohorts (log-rank P = 0.003; HR = 1.96; P = 0.004). Importantly, patients with ESCC with high levels of F. nucleatum displayed poor chemotherapeutic response for all three evaluation methods: RECIST (P = 0.04), SUVmax change in PET/CT (P = 0.0004), and TRG (P = 0.003).Conclusions: We conclude that high levels of intratumoral F. nucleatum have a prognostic significance for predicting poor RFS in patients with ESCC. More importantly, our data indicates that higher F. nucleatum burden correlates with poor response to neoadjuvant chemotherapy, suggesting the possibility that an antibiotic intervention against this bacterium may significantly improve therapeutic response in patients with ESCC.