Research Paper Volume 13, Issue 3 pp 4258—4273
Cross-platform genomic identification and clinical validation of breast cancer diagnostic biomarkers
- 1 Department of Laboratory Science, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, P.R. China
- 2 Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China
- 3 Department of Respiratory, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, P.R. China
- 4 Guangzhou Mendel Genomics and Medical Technology Co., Ltd., Guangzhou 510530, P.R. China
- 5 Department of Laboratory Science, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518000, P.R. China
- 6 Department of Laboratory Science, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan 528300, P.R. China
Received: October 3, 2020 Accepted: November 23, 2020 Published: January 20, 2021https://doi.org/10.18632/aging.202388
How to Cite
Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction: Circulating non-coding RNA is an ideal source to discover novel biomarkers for non-invasive screening. However, studies for the discovery of universal miRNAs in serum and exosomes for breast cancer early diagnosis are limited.
Methods: Based on bioinformatic analysis, in vitro and in vivo studies were performed to understand the role of identified hsa-miR-423-5p in cancer proliferation, migration, cancer stem cell properties. Next, global non-coding RNA expression profiles in blood serum and exosome were performed. hsa-miR-423-5p expression from a total of 356 peripheral blood samples was evaluated and the association of hsa-miR-423-5p expression with clinical characteristics, sensitivity and specificity for breast cancer diagnosis were assessed.
Results: The expression of serum and exosomal hsa-miR-423-5p is abnormally increased in breast cancer. Suppression of hsa-miR-423-5p inhibited cell proliferation and invasion in both T47D and MDA-MB-231 breast cancer cell lines, and tumor growth in vivo. Compared with 113 healthy women, quantification analysis of hsa-miR-423-5p in 224 breast cancer samples confirmed the abnormal expression. Serum hsa-miR-423-5p was significantly associated with the clinical stage (P=0.001) and Ki-67 level (P=0.004).
Conclusions: A translational bioinformatics analysis procedure and validation by in vitro, in vivo, and clinical samples reveal that hsa-miR-423-5p could be used as a non-invasive breast cancer biomarker.
AUC: area under curve; CCLE: The Cancer Cell Line Encyclopedia; FPKM: fragments per kilobase per million reads; GEO: Gene Expression Omnibus; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MHC: major histocompatibility complex; qRT-PCR: quantitative real-time polymerase chain reaction; ROC: receiver operating characteristic curve; TCGA: The Cancer Genome Atlas.