Wang Fangqing, Fan Jinlei, Lu Fei, Xu Janwei, Zhang Hui, Han Junqi, Chen Jingjing, Yu Dexin
Department of Radiology, Qilu Hospital, Shandong University, Jinan, China.
School of Medical Imaging, Shandong Second Medical University, Weifang, China.
Quant Imaging Med Surg. 2025 Jan 2;15(1):662-675. doi: 10.21037/qims-24-103. Epub 2024 Dec 17.
Hypoxia-inducible factor-1-alpha (HIF-1α) has the potential to predict the neoadjuvant chemotherapy (NAC) response in pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the relationship between the pathological response and intratumoral HIF-1α expression in patients with PDAC receiving NAC, and investigate the predictive value of contrast-enhanced computed tomography (CECT) features in HIF-1α expression.
A total of 58 patients from three centers with pathologically confirmed PDAC who underwent NAC followed by surgery were retrospectively enrolled in this study. Immunohistochemistry was performed to detect intratumoral HIF-1α expression. The Chi-square test was used to evaluate the differences in intratumoral HIF-1α expression in PDAC responders and non-responders after NAC. Binary logistic regression and receiver operating characteristic (ROC) curves were used to determine the optimal correlation factors of different pathological responses in PDAC patients after NAC and to predict these factors using CECT features.
Among the PDAC patients, 27 (46.55%) responders and 31 (53.45%) non-responders were identified via histopathological examination. Nuclear and cytoplasmic HIF-1α expression was significantly higher in the responders than the non-responders (P<0.001, P=0.036). However, HIF-1α expression in the stroma was not statistically significant (P=0.864). The multivariate logistic regression revealed that the %Δ carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and nuclear HIF-1α were independent predictors of different pathological responses [odds ratio (OR) =9.005, P=0.037; OR =0.005, P=0.044; OR =0.352, P=0.018, respectively]. The ROC curve showed that nuclear HIF-1α expression was the optimal associated predictor of the pathologic response (area under the curve =0.873, 95% confidence interval: 0.782-0.964). The multivariate logistic regression also showed that of the CECT characteristics, the (post-NAC - pre-NAC) arterial phase (AP) was an independent predictive indicator of nuclear HIF-1α expression (OR =1.012, P=0.020).
Nuclear HIF-1α was the best predictor of the pathological response in patients with PDAC after NAC, and it can be predicted using CT feature of the (post-NAC - pre-NAC) AP.
缺氧诱导因子-1α（HIF-1α）有可能预测胰腺导管腺癌（PDAC）的新辅助化疗（NAC）反应。本研究旨在评估接受NAC的PDAC患者的病理反应与肿瘤内HIF-1α表达之间的关系，并研究对比增强计算机断层扫描（CECT）特征对HIF-1α表达的预测价值。
本研究回顾性纳入了来自三个中心的58例经病理证实为PDAC且接受了NAC随后进行手术的患者。采用免疫组织化学法检测肿瘤内HIF-1α表达。采用卡方检验评估NAC后PDAC反应者和无反应者肿瘤内HIF-1α表达的差异。采用二元逻辑回归和受试者工作特征（ROC）曲线确定NAC后PDAC患者不同病理反应的最佳相关因素，并使用CECT特征预测这些因素。
在PDAC患者中，通过组织病理学检查确定了27例（46.55%）反应者和31例（53.45%）无反应者。反应者的核HIF-1α和细胞质HIF-1α表达显著高于无反应者（P<0.001，P=0.036）。然而，基质中HIF-1α的表达无统计学意义（P=0.864）。多因素逻辑回归显示，糖类抗原19-9（CA19-9）变化百分比、肿瘤分化程度和核HIF-1α是不同病理反应的独立预测因素[比值比（OR）分别为9.005，P=0.037；OR =0.005，P=0.044；OR =0.352，P=0.018]。ROC曲线显示，核HIF-1α表达是病理反应的最佳相关预测指标（曲线下面积=0.873，95%置信区间：0.782-0.964）。多因素逻辑回归还显示，在CECT特征中，（NAC后 - NAC前）动脉期（AP）是核HIF-1α表达的独立预测指标（OR =1.012，P=0.020）。
核HIF-1α是NAC后PDAC患者病理反应的最佳预测指标，并且可以使用（NAC后 - NAC前）AP的CT特征进行预测。
