Early detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes; however, PDAC is usually diagnosed late. Therefore, blood-based minimally invasive biomarker assays for limited volume clinical samples are urgently needed. A novel miRNA profiling platform (Abcam Fireplex-Oncology Panel) was used to investigate the feasibility of developing early detection miRNA biomarkers with 20 μL plasma from a training set (58 stage II PDAC cases and 30 controls) and two validation sets (34 stage II PDAC cases and 25 controls; 44 stage II PDAC cases and 18 controls). miR-34a-5p [AUC = 0.77; 95% confidence interval (CI), 0.66–0.87], miR-130a-3p (AUC = 0.74; 95% CI, 0.63–0.84), and miR-222-3p (AUC = 0.70; 95% CI, 0.58–0.81) were identified as significantly differentially abundant in plasma from stage II PDAC versus controls. Although none of the miRNAs individually outperformed the currently used serologic biomarker for PDAC, carbohydrate antigen 19-9 (CA19-9), combining the miRNAs with CA 19-9 improved AUCs from 0.89 (95% CI, 0.81–0.95) for CA 19-9 alone to 0.92 (95% CI, 0.86–0.97), 0.94 (95% CI, 0.89–0.98), and 0.92 (95% CI, 0.87–0.97), respectively. Gene set enrichment analyses of transcripts correlated with high and low expression of the three miRNAs in The Cancer Genome Atlas PDAC sample set. These miRNA biomarkers, assayed in limited volume plasma together with CA19-9, discriminate stage II PDAC from controls with good sensitivity and specificity. Unbiased profiling of larger cohorts should help develop an informative early detection biomarker assay for diagnostic settings. Prevention Relevance: Development of minimally invasive biomarker assays for detection of premalignant disease and early-stage pancreatic cancer is key to improving patient survival. This study describes a limited volume plasma miRNA biomarker assay that can detect early-stage resectable pancreatic cancer in clinical samples necessary for effective prevention and clinical intervention.

中文翻译：

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用于检测早期胰腺癌的有限体积样本中的血浆 miRNA 生物标志物

早期发现胰腺导管腺癌 (PDAC) 是改善患者预后的关键；然而，PDAC 通常诊断较晚。因此，迫切需要对有限体积的临床样本进行基于血液的微创生物标志物测定。一个新的 miRNA 分析平台（Abcam Fireplex-Oncology Panel）被用于研究开发早期检测 miRNA 生物标志物的可行性，其中 20 μL 血浆来自一个训练集（58 个 II 期 PDAC 病例和 30 个对照）和两个验证集（34 个 II 期） PDAC 病例和 25 个对照；44 个 II 期 PDAC 病例和 18 个对照）。miR-34a-5p [AUC = 0.77; 95% 置信区间 (CI), 0.66–0.87], miR-130a-3p (AUC = 0.74; 95% CI, 0.63–0.84) 和 miR-222-3p (AUC = 0.70; 95% CI, 0.58–0.81) ) 被鉴定为在 II 期 PDAC 与对照的血浆中存在显着差异。尽管没有一个 miRNA 单独优于目前使用的 PDAC 血清学生物标志物、碳水化合物抗原 19-9 (CA19-9)，但将 miRNA 与 CA 19-9 组合将 CA 19 的 AUC 从 0.89 (95% CI, 0.81–0.95) 提高-9 分别为 0.92（95% CI，0.86–0.97）、0.94（95% CI，0.89–0.98）和 0.92（95% CI，0.87–0.97）。转录本的基因集富集分析与癌症基因组图谱 PDAC 样本集中三种 miRNA 的高表达和低表达相关。这些 miRNA 生物标志物与 CA19-9 一起在有限体积的血浆中进行测定，以良好的敏感性和特异性将 II 期 PDAC 与对照区分开来。对更大的队列进行无偏见的分析应该有助于开发用于诊断环境的信息丰富的早期检测生物标志物测定。预防相关：开发用于检测癌前疾病和早期胰腺癌的微创生物标志物检测是提高患者生存率的关键。本研究描述了一种有限体积的血浆 miRNA 生物标志物测定法，该测定法可以检测有效预防和临床干预所必需的临床样本中的早期可切除胰腺癌。