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. 2021 Jun 10;11:12298. doi: 10.1038/s41598-021-91804-0

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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The expression levels of miR-1246 and miR-451a in serum EVs and tissues, and the potential for the application of these miRNAs as diagnostic biomarkers for gallbladder cancer. (a) The miR-1246 expression levels in serum EVs in the GBC were significantly higher in comparison to the Benign and the HCs (P = 0.005), while the miR-451a expression levels in the GBC were significantly lower in comparison to the Benign and HCs (P = 0.001). (b) The miR-1246 was significantly upregulated in gallbladder cancer tissues in comparison to normal tissue (FC = 1.79, P = 0.029), and the miR-451a was significantly downregulated in the cancer tissues in comparison to normal tissue (FC = 0.022, P < 0.001) in GSE 104165 from GEO dataset. (c) The expression levels of miR-1246 were significantly higher in GBC patients with stage IIIB–IV in comparison to the Benign and HCs, but not in patients with stage 0–IIIA. Similarly, the miR-451a expression levels was significantly lower in GBC patients with stage III–IV, but not those with stage 0–II, in comparison to the Benign and the HCs. (d) The receiver-operating characteristic (ROC) curve analysis of miR-1246, miR-451a, CEA, and CA19-9 for discriminating GBC from Benign and HCs. These curves revealed that the optimal combination was CEA, CA19-9 and miR-1246 in serum EVs (sensitivity, 72.0%; specificity, 90.8%; accuracy, 81.7%; AUC, 0.816 [95% confidence interval, 0.712–0.888]). *P < 0.05 and **P < 0.01.