Background

A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease.

Aims

Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients.

Methods

The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction.

Results

We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956–0.987) and 0.924 (95% CI 0.899–0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%.

Conclusions

A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.

Graphical Abstract

中文翻译：

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开发基于血清的 MicroRNA 特征用于早期检测胰腺癌：一项多中心队列研究

背景

胰腺癌（PCa）的严峻预后归因于该疾病的早期诊断困难。

目标

因此，迫切需要确定新的生物标志物来早期检测前列腺癌，以提高患者的总体生存率。

方法

该研究首先使用微阵列图谱在福尔马林固定、石蜡包埋的组织中鉴定候选 microRNA (miRNA)，然后在基于血清的队列研究中进行验证，以评估候选药物的临床效用。在队列中，来自四个中心的总共 1273 名参与者被回顾性招募为两个队列，包括训练队列和验证队列。通过实时聚合酶链反应对收集的血清标本进行分析。

结果

我们鉴定出 27 个 miRNA 在 PCa 组织中与良性组织相比有差异表达。其中，选取前四名作为在血清标本中充分评估诊断效果的小组。该小组在区分早期 PCa 患者与健康对照或非 PCa（包括慢性胰腺炎和胰腺囊性肿瘤）方面优于 CA19-9、CA125、CEA 和 CA242，曲线下面积 (AUC) 为 0.971（ 95% CI 0.956–0.987) 和 0.924 (95% CI 0.899–0.949)。此外，该小组还消除了其他消化道肿瘤的干扰，特异性为 90.2%。

结论

开发了一组由四种血清 miRNA 组成的组，显示出早期 PCa 与健康对照或其他胰腺疾病的显着区分能力，表明它可以开发为临床早期筛查 PCa 的新型非侵入性方法。

图形概要