Braadland Peder R, Farnes Ingvild, Kure Elin H, Yaqub Sheraz, McCann Adrian, Ueland Per M, Labori Knut Jørgen, Hov Johannes R
Research Institute of Internal Medicine and Norwegian PSC Research Center, Division of Surgery and Specialized Medicine, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Front Oncol. 2024 Dec 20;14:1488749. doi: 10.3389/fonc.2024.1488749. eCollection 2024.
BACKGROUND/AIMS: It was recently reported that a higher concentration of the bacterially produced metabolite indole 3-acetate (3-IAA) in blood was linked to a better response to chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to extend these observations to patients diagnosed with non-metastatic PDAC.
We measured circulating 3-IAA in samples from a prospective population-based cohort of 124 patients with borderline resectable or locally advanced PDAC, collected before initiating neoadjuvant chemotherapy. The majority (61%) of the patients were treated with FOLFIRINOX. We used univariable and multivariable Cox proportional hazards regression to estimate the association between pre-treatment 3-IAA and overall survival.
The median serum 3-IAA concentration before chemotherapy was 290 (interquartile range 203-417) ng/mL. The unadjusted hazard ratio (HR) for pre-treatment log(3-IAA) was 0.93, 95% confidence interval (CI) [0.74-1.16], p=0.52. When adjusting for age, ECOG, CA19-9 and tumor classification, the HR for log(3-IAA) was 0.87, 95% CI [0.68-1.12], p=0.28.
Our findings suggest that the potentiating effect of 3-IAA observed in metastatic PDAC undergoing chemotherapy may not translate to borderline resectable or locally advanced PDAC. We recommend additional clinical validation of 3-IAA's predictive value in different categories of PDAC before implementation attempts in human studies are initiated.
背景/目的：最近有报道称，血液中细菌产生的代谢产物吲哚-3-乙酸（3-IAA）浓度较高与转移性胰腺导管腺癌（PDAC）患者对化疗的更好反应相关。在此，我们旨在将这些观察结果扩展至诊断为非转移性PDAC的患者。
我们测量了来自一个基于人群的前瞻性队列中124例临界可切除或局部晚期PDAC患者样本中的循环3-IAA，这些样本是在开始新辅助化疗之前采集的。大多数（61%）患者接受了FOLFIRINOX治疗。我们使用单变量和多变量Cox比例风险回归来估计治疗前3-IAA与总生存期之间的关联。
化疗前血清3-IAA浓度中位数为290（四分位间距203 - 417）ng/mL。治疗前log(3-IAA)的未调整风险比（HR）为0.93，95%置信区间（CI）[0.74 - 1.16]，p = 0.52。在调整年龄、ECOG、CA19-9和肿瘤分类后，log(3-IAA)的HR为0.87，95% CI [0.68 - 1.12]，p = 0.28。
我们的研究结果表明，在接受化疗的转移性PDAC中观察到的3-IAA的增强作用可能不适用于临界可切除或局部晚期PDAC。我们建议在启动人体研究实施尝试之前，对3-IAA在不同类型PDAC中的预测价值进行额外的临床验证。
