Identification of Candidate miRNA Biomarkers for Glaucoma

被引:67
|
作者
Hindle, Allyson G. [1 ,2 ]
Thoonen, Robrecht [2 ,3 ,4 ]
Jasien, Jessica, V [5 ]
Grange, Robert M. H. [1 ,2 ]
Amin, Krishna [6 ]
Wise, Jasen [6 ]
Ozaki, Mineo [7 ]
Ritch, Robert [5 ]
Malhotra, Rajeev [2 ,3 ,4 ]
Buys, Emmanuel S. [1 ,2 ]
机构
[1] Massachusetts Gen Hosp, Res Inst, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA
[2] Harvard Med Sch, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Res Inst, Cardiovasc Res Ctr, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Res Inst, Cardiol Div, Dept Med, Boston, MA 02114 USA
[5] New York Ear Eye & Ear Infirm Mt Sinai, Einhorn Clin Res Ctr, New York, NY USA
[6] Qiagen, Frederick, MD USA
[7] Ozaki Eye Hosp, Miyazaki, Japan
关键词
glaucoma; microRNA; aqueous humor; plasma; biomarker; OPEN-ANGLE GLAUCOMA; TRABECULAR MESHWORK CELLS; HUMAN AQUEOUS-HUMOR; NITRIC-OXIDE; INTRAOCULAR-PRESSURE; GUANYLATE-CYCLASE; COMMON VARIANTS; MICRORNA; PATHWAY; MARKER;
D O I
10.1167/iovs.18-24878
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. Glaucoma, a leading cause of blindness worldwide, often remains undetected until irreversible vision loss has occurred. Treatments focus on lowering intraocular pressure (IOP), the only modifiable and readily measurable risk factor. However, IOP can vary and does not always predict disease progression. MicroRNAs (miRNAs) are promising biomarkers. They are abundant and stable in biological fluids, including plasma and aqueous humor (AqH). We aimed to identify differentially expressed miRNAs in AqH and plasma from glaucoma, exfoliation syndrome (XFS), and control subjects. METHODS. Plasma and AqH from two ethnic cohorts were harvested from glaucoma or XFS (often associated with glaucoma, n = 33) and control (n = 31) patients undergoing elective surgery. A custom miRNA array measured 372 miRNAs. Molecular target prediction and pathway analysis were performed with Ingenuity Pathway Analysis (IPA) and DIANA bioinformatical tools. RESULTS. Levels of miRNAs in plasma, a readily accessible biomarker source, correlated with miRNA levels in AqH. Twenty circulating miRNAs were at least 1.5-fold higher in glaucoma or XFS patients than in controls across two ethnic cohorts: miR-4667-5p (P = 4.1 3 10(-5)), miR99b- 3p (P = 4.8 3 10(-5)), miR-637 (P = 5.1 3 10(-5)), miR-4490 (P = 5.7 3 10(-5)), miR-1253 (P = 6.0 3 10(-5)), miR-3190-3p (P = 3.1 3 10-4), miR-3173-3p (P = 0.001), miR-608 (P = 0.001), miR-4725-3p (P = 0.002), miR-4448 (P = 0.002), and miR-323b-5p (P = 0.002), miR4538 (P = 0.003), miR-3913-3p (P = 0.003), miR-3159 (P = 0.003), miR-4663 (P = 0.003), miR-4767 (P = 0.003), miR-4724-5p (P = 0.003), miR-1306-5p (P = 0.003), miR-181b-3p (P = 0.004), and miR-433-3p (P = 0.004). miR-637, miR-1306-5p, and miR-3159, in combination, allowed discrimination between glaucoma patients and control subjects (AUC = 0.91 6 0.008, sensitivity 85.0%, specificity 87.5%). CONCLUSIONS. These results identify specific miRNAs as potential biomarkers and provide insight into the molecular processes underlying glaucoma.
引用
收藏
页码:134 / 146
页数:13
相关论文
共 50 条
  • [31] Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches
    Lu, Wei
    Wang, Qiang
    Xue, Yi
    Gu, Jie
    Yao, Ping
    Ge, Yufan
    Miao, Yiming
    Chen, Jun
    Computational and Mathematical Methods in Medicine, 2021, 2021
  • [32] Luminal A breast cancer: identification of novel circulating miRNA biomarkers
    McDermott, A. M.
    Miller, N.
    Ball, G.
    Sweeney, K. J.
    Kerin, M. J.
    CANCER RESEARCH, 2012, 72
  • [33] miRNA expression profiling for identification of potential breast cancer biomarkers
    Tjensvoll, Kjersti
    Svendsen, Kine N.
    Reuben, James M.
    Oltedal, Satu
    Gilje, Bjornar
    Smaaland, Rune
    Nordgard, Oddmund
    BIOMARKERS, 2012, 17 (05) : 463 - 470
  • [34] IDENTIFICATION OF PERIPHERAL miRNA BIOMARKERS IMPLICATED IN THE DEFAULT MODE NETWORK
    Carless, Melanie
    Kumar, Ashish
    Clarke, Geoffrey
    Puppala, Sobha
    Cruz, Dianne
    Nathanielsz, Peter
    Kent, Jack
    Li, Cun
    Bliss-Moreau, Eliza
    Kos, Mark
    EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2019, 29 : 1143 - 1144
  • [35] Identification of potential miRNA biomarkers for traumatic osteonecrosis of femoral head
    Liu, Guan-Zhi
    Chen, Chen
    Kong, Ning
    Tian, Run
    Li, Yi-Yang
    Li, Zhe
    Wang, Kun-Zheng
    Yang, Pei
    JOURNAL OF CELLULAR PHYSIOLOGY, 2020, 235 (11) : 8129 - 8140
  • [36] Identification of Potential miRNA Biomarkers to Detect Hydrocortisone Administration in Horses
    Kikuchi, Mio
    Ishige, Taichiro
    Minamijima, Yohei
    Hirota, Kei-ichi
    Nagata, Shun-ichi
    Tozaki, Teruaki
    Kakoi, Hironaga
    Ishiguro-Oonuma, Toshina
    Kizaki, Keiichiro
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (19)
  • [37] Identification of serum exosomal miRNA biomarkers for diagnosis of Rheumatoid arthritis
    Gong, Jianmin
    Zhang, Xiaoshan
    Khan, Adeel
    Liang, Jun
    Xiong, Tao
    Yang, Ping
    Li, Zhiyang
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2024, 129
  • [38] Identification of Potential Osteoporosis miRNA Biomarkers Using Bioinformatics Approaches
    Lu, Wei
    Wang, Qiang
    Xue, Yi
    Gu, Jie
    Yao, Ping
    Ge, Yufan
    Miao, Yiming
    Chen, Jun
    COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE, 2021, 2021
  • [39] In silico identification of candidate miRNA-encoded Peptides in four Fabaceae
    de Araujo, Paula Machado
    Grativol, Clicia
    COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2022, 97
  • [40] Identification of candidate targets and mechanisms involved in miRNA regulation in multiple myeloma
    Yang, Yang
    Ding, Rong
    Wang, Rui
    WORLD JOURNAL OF SURGICAL ONCOLOGY, 2022, 20 (01)