Blomstrand Hakon, Bodarve Malin, Groth Fredrik, Naredi Peter, Sund Malin, Vilhav Caroline, Green Henrik, Björnsson Bergthor, Öhlund Daniel, Lindblad Stina, Franklin Oskar, Elander Nils O
Division of Surgery, Orthopaedics and Oncology, Department of Biomedical and Clinical Sciences, Linköping University, SE-58185 Linköping, Sweden.
Department of Clinical Pathology, Linköping University Hospital, SE-58185 Linköping, Sweden.
Oncol Lett. 2024 Dec 10;29(2):99. doi: 10.3892/ol.2024.14845. eCollection 2025 Feb.
Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and biomarkers to guide treatment decisions in PDAC are generally lacking. Intratumoural expression of dihydropyrimidine dehydrogenase (DPD) is a potential prognostic parameter in patients with PDAC undergoing surgical resection and postoperative chemotherapy. In the present study, DPD was analysed by immunohistochemistry of a tissue microarray platform including a real-world cohort of 495 patients with PDAC who had undergone resection with curative intent at any of three tertiary centres, including Northern, Western and Southeastern regions of Sweden, between 1993 and 2019. DPD level (high/low) was analysed and overall survival associations were assessed in treatment subgroups using a multivariate Cox regression model accounting for potential confounders. In patients who had not received adjuvant chemotherapy (n=182), the median overall survival time was 11.6 months (95% CI 9.6-13.5), compared with 28.8 months (25.0-32.6) among those who had (n=313; log-rank P<0.001). The most common type of chemotherapy was gemcitabine single agent (Gem, n=239) followed by gemcitabine plus capecitabine (GemCape, n=39). Tumour-Node-Metastasis (TNM) stage and DPD expression were statistically significant prognostic parameters in the Gem group (HR 1.19, 95% CI 1.01-1.41, P=0.036), with high expression of DPD linked with worse survival. In addition, tumour grade and TNM stage were statistically significant prognostic factors in the group that did not receive any chemotherapy (P≤0.001). No statistically significant parameters were identified in the GemCape group. Taken together, intratumoural expression of DPD may be considered a prognostic marker for patients with PDAC treated with adjuvant gemcitabine following surgical resection, with low expression levels predicting better survival. Further studies in larger cohorts of patients receiving multi-drug or non-gemcitabine based regimens are warranted.
胰腺导管腺癌（PDAC）预后较差，目前普遍缺乏可指导PDAC治疗决策的生物标志物。肿瘤内二氢嘧啶脱氢酶（DPD）的表达是接受手术切除和术后化疗的PDAC患者的一个潜在预后参数。在本研究中，通过组织微阵列平台的免疫组织化学分析DPD，该平台纳入了1993年至2019年间在瑞典北部、西部和东南部三个三级中心之一接受根治性切除的495例PDAC患者的真实世界队列。分析DPD水平（高/低），并使用多变量Cox回归模型评估治疗亚组中的总生存相关性，该模型考虑了潜在的混杂因素。未接受辅助化疗的患者（n = 182）的中位总生存时间为11.6个月（95%CI 9.6 - 13.5），而接受辅助化疗的患者（n = 313）为28.8个月（25.0 - 32.6）（对数秩检验P < 0.001）。最常见的化疗类型是吉西他滨单药治疗（Gem，n = 239），其次是吉西他滨联合卡培他滨（GemCape，n = 39）。在Gem组中，肿瘤-淋巴结-转移（TNM）分期和DPD表达是具有统计学意义的预后参数（HR 1.19，95%CI 1.01 - 1.41，P = 0.036），DPD高表达与较差的生存率相关。此外，在未接受任何化疗的组中，肿瘤分级和TNM分期是具有统计学意义的预后因素（P≤0.001）。在GemCape组中未发现具有统计学意义的参数。综上所述，肿瘤内DPD表达可被视为手术切除后接受辅助吉西他滨治疗的PDAC患者的预后标志物，低表达水平预示着更好的生存率。有必要对接受多药或非吉西他滨方案治疗的更大患者队列进行进一步研究。
