Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Surgery, Osaka Police Hospital, Osaka, Japan.
PLoS One. 2024 Sep 17;19(9):e0310328. doi: 10.1371/journal.pone.0310328. eCollection 2024.
Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after radical resection because of subclinical tumors. To manage them, a reliable biomarker that can indicate the presence of subclinical tumors and predict their chemosensitivity is required. This study aimed to identify a miRNA as a biomarker that can be used to individualize postoperative adjuvant chemotherapy using postoperative peripheral blood samples. Integrating miRNA microarray data from the blood of 18 patients with PDAC and the in vitro results regarding the phenotypes of chemoresistant PDAC cells, a candidate miRNA was identified. The relationships between candidate miRNA expression and chemosensitivity were examined in vitro and in clinical samples from other cohorts of 33 patients with recurrence. Comprehensive analyses of blood samples detected 5 candidate miRNAs. Of these, miR-26a-5p was considered a candidate biomarker of chemosensitive phenotypes. In validation experiments, chemosensitivity was inversely correlated with miR-26a-5p expression in vitro. Moreover, the ability of miR-26a-5p to predict chemosensitivity was clinically evaluated using blood samples. Patients with high miR-26a-5p expression in the blood after radical resection exhibited a significantly longer survival time after recurrence. Thus, we concluded that miR-26a-5p is a potentially useful biomarker for managing patients with PDAC, especially those undergoing adjuvant chemotherapy.
胰腺导管腺癌(PDAC)即使在根治性切除术后仍有很高的复发率,这是因为存在亚临床肿瘤。为了管理这些肿瘤,需要一种可靠的生物标志物,能够指示亚临床肿瘤的存在并预测其化疗敏感性。本研究旨在鉴定一种 miRNA 作为生物标志物,用于使用术后外周血样本对接受根治性手术的患者进行个体化辅助化疗。整合了 18 例 PDAC 患者的血液 miRNA 微阵列数据和体外关于化疗耐药 PDAC 细胞表型的结果,鉴定出候选 miRNA。在体外和另外 33 例复发患者的其他队列的临床样本中,研究了候选 miRNA 表达与化疗敏感性之间的关系。对血液样本进行了综合分析,检测到 5 种候选 miRNA。其中,miR-26a-5p 被认为是化疗敏感表型的候选生物标志物。在验证实验中,miR-26a-5p 的表达与体外的化疗敏感性呈负相关。此外,还使用血液样本对 miR-26a-5p 预测化疗敏感性的能力进行了临床评估。在根治性手术后血液中 miR-26a-5p 表达较高的患者,在复发后生存时间显著延长。因此,我们得出结论,miR-26a-5p 是一种用于管理 PDAC 患者,特别是接受辅助化疗患者的潜在有用的生物标志物。