HIF-1α expression is associated with the pathological response to neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma patients and can be predicted using CECT features.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.