Tavano Francesca, Fontana Andrea, Mazza Tommaso, Gioffreda Domenica, Biagini Tommaso, Palumbo Orazio, Carella Massimo, Andriulli Angelo
Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, Italy.
Unit of Biostatistics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, Italy.
Front Oncol. 2020 Sep 11;10:1567. doi: 10.3389/fonc.2020.01567. eCollection 2020.
The high prevalence of early-diabetes in patients with pancreatic cancer (PanC) implies that its recognition could help identify people at high risk of developing PanC. Candidate microRNAs (miRNAs) associated with recent diabetes were screened from our previous miRNA expression profiling on 10 pools of plasma from PanC patients and non-PanC controls, both including also subjects with early- and late-diabetes. The droplet digital PCR (ddPCR) was used to re-test candidate miRNAs in a new independent cohort of 69 subjects (40 PanC, 29 non-PanC) with early- (17 PanC, 13 non-PanC) or late-diabetes (23 PanC, 16 non-PanC), and in 100 non-diabetic healthy subjects (HS). miRNA levels were evaluated for differences between subjects enrolled into the study and for their diagnostic performance, also compared to the CA 19-9 determinations. MiR-20b-5p, miR-29a, and miR-18a-5p were selected from the previous miRNA expression profiling. The ddPCR confirmed the increase of miR-20b-5p and miR-29a levels in PanC with early- compared to those with late-diabetes. Conversely, miR-20b-5p, miR-29a, and miR-18a-5p were over-expressed in both PanC and non-PanC with recent diabetes compared to HS, and each miRNA achieved a similar diagnostic performance in distinguishing either PanC or non-PanC with early-diabetes from HS (miR-20b-5p: AUC = 0.877 vs. AUC = 0.873; miR-29a: AUC = 0.838 vs. AUC = 0.810; miR-18a-5p: AUC = 0.824 vs. AUC = 0.875). Despite miR-20b-5p and miR-29a expressions were also higher both in PanC and non-PanC with late-diabetes with respect to HS, the diagnostic accuracy in PanC with late-diabetes vs. HS reached by each miRNA (miR-20b-5p: AUC = 0.760; miR-29a: AUC = 0.630) was lower than the ones achieved in PanC with early-diabetes vs. HS. Furthermore, miR-20b-5p achieved a higher diagnostic accuracy to discriminate non-PanC with early-diabetes from HS (AUC = 0.868; SP = 81%; PPV = 32.1%) compared to the CA 19-9 (AUC = 0.700; SP = 40.0%; PPV = 15.5%), and the joint (miR-20b-5p and CA 19-9) discrimination ability was higher than the one achieved by the CA 19-9 tested alone (AUC = 0.900, = 0.003). Our data highlighted the association between miR-18a-5p and early-diabetes, and suggested for miR-20b-5p and miR-29 a role in identifying early diabetes in PanC, albeit not as an early manifestation of cancer. MiR-20b-5p as more informative marker than CA 19-9 in distinguishing non-PanC with recent diabetes from HS was also uncovered.
胰腺癌（PanC）患者中早期糖尿病的高患病率表明，对其进行识别有助于确定患胰腺癌风险较高的人群。我们先前对10组胰腺癌患者和非胰腺癌对照者的血浆进行了miRNA表达谱分析，从中筛选出与近期糖尿病相关的候选微小RNA（miRNA），这些样本中既有早期糖尿病患者，也有晚期糖尿病患者。采用液滴数字PCR（ddPCR）对一个新的独立队列中的候选miRNA进行重新检测，该队列包括69名受试者（40例胰腺癌患者、29例非胰腺癌患者），其中有早期糖尿病患者（17例胰腺癌患者、13例非胰腺癌患者）或晚期糖尿病患者（23例胰腺癌患者、16例非胰腺癌患者），还有100名非糖尿病健康受试者（HS）。评估了miRNA水平在纳入研究的受试者之间的差异及其诊断性能，并与CA 19-9测定结果进行比较。从先前的miRNA表达谱分析中选出了miR-20b-5p、miR-29a和miR-18a-5p。ddPCR证实，与晚期糖尿病患者相比，早期糖尿病胰腺癌患者中miR-20b-5p和miR-29a水平升高。相反，与健康受试者相比，近期患糖尿病的胰腺癌患者和非胰腺癌患者中miR-20b-5p、miR-29a和miR-18a-5p均过表达，并且每种miRNA在区分早期糖尿病的胰腺癌患者或非胰腺癌患者与健康受试者方面具有相似的诊断性能（miR-20b-5p：AUC = 0.877 vs. AUC = 0.873；miR-29a：AUC = 0.838 vs. AUC = 0.810；miR-18a-5p：AUC = 0.824 vs. AUC = 0.875）。尽管与健康受试者相比，晚期糖尿病的胰腺癌患者和非胰腺癌患者中miR-20b-5p和miR-29a的表达也较高，但每种miRNA在区分晚期糖尿病胰腺癌患者与健康受试者时的诊断准确性（miR-20b-5p：AUC = 0.760；miR-29a：AUC = 0.630）低于区分早期糖尿病胰腺癌患者与健康受试者时的诊断准确性。此外，与CA 19-9相比，miR-20b-5p在区分早期糖尿病非胰腺癌患者与健康受试者方面具有更高的诊断准确性（AUC = 0.868；SP = 81%；PPV = 32.1%），而联合（miR-20b-5p和CA 19-9）判别能力高于单独检测CA 19-9时的判别能力（AUC = 0.900，P = 0.003）。我们的数据突出了miR-18a-5p与早期糖尿病之间的关联，并表明miR-20b-5p和miR-29a在识别胰腺癌中的早期糖尿病方面发挥作用，尽管这并非癌症的早期表现。还发现miR-20b-5p在区分近期患糖尿病的非胰腺癌患者与健康受试者方面比CA 19-9更具信息价值。
