Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Research and Development Division, ARKRAY, Inc., Yousuien-nai, 59 Gansuin-cho, Kamigyo-ku, Kyoto, Japan.
Br J Cancer. 2024 Oct;131(7):1158-1168. doi: 10.1038/s41416-024-02794-5. Epub 2024 Aug 28.
Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers.
We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort.
The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%).
We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer.
胰腺癌通常在晚期被诊断,由于症状不特异且缺乏可用的生物标志物,早期诊断胰腺癌较为困难。
我们对来自 14 家医院的 212 例胰腺癌患者样本和 213 例非癌健康对照样本进行了全面的血清 miRNA 测序。我们将胰腺癌和对照样本随机分为两个队列:训练队列(N=185)和验证队列(N=240)。我们创建了结合自动机器学习和 100 个高表达 miRNA 的组合模型,并与 CA19-9 相结合,验证了模型在独立验证队列中的性能。
结合 100 个高表达 miRNA 和 CA19-9 的诊断模型能够以高精度区分胰腺癌与非癌健康对照(曲线下面积(AUC)为 0.99;敏感性为 90%;特异性为 98%)。我们在独立的无症状早期(0 期-I 期)胰腺癌队列中验证了高诊断准确性(AUC:0.97;敏感性为 67%;特异性为 98%)。
我们证明了这 100 个高表达 miRNA 及其与 CA19-9 的组合可以作为特异性和早期检测胰腺癌的生物标志物。