Transcriptional profiling analysis predicts potential biomarkers for glaucoma: HGF, AKR1B10 and AKR1C3

Nie,Qiaoli; Zhang,Xiaoyan

doi:10.3892/etm.2018.6875

Transcriptional profiling analysis predicts potential biomarkers for glaucoma: HGF, AKR1B10 and AKR1C3

Authors:
- Qiaoli Nie
- Xiaoyan Zhang
View Affiliations

Affiliations: Department of Ophthalmology, The Second People's Hospital of Jinan, Jinan, Shandong 250001, P.R. China, Department of Ophthalmology, The People's Hospital of Shouguang, Weifang, Shandong 262700, P.R. China
Published online on: October 17, 2018 https://doi.org/10.3892/etm.2018.6875
Pages: 5103-5111

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glaucoma results in damage to the optic nerve and vision loss. The aim of this study was to screen more accurate biomarkers and targets for glaucoma. The datasets E-GEOD-7144 and E-MEXP-3427 were screened for differently expressed genes (DEGs) by significance analysis of microarrays. Functional and pathway enrichment analysis were processed. Pathway relationship networks and gene co-expression networks were constructed. DEGs of disease and treatment with the same symbols were of interest. RT-qPCR was processed to verify the expression of key DEGs. A total of 1,019 DEGs of glaucoma were identified and 93 DEGs in transforming growth factor-β1 (TGF-β1) and TGF-β1-2 treatment cases compared with the normal control group. Pathway relationship network of glaucoma was constructed with 25 nodes. The pathway relationship network of TGF-β1 and -2 treatment groups was constructed with 11 nodes. Glaucoma‑related DEGs in GO terms and pathways were inserted and 180 common DEGs were obtained. Then, gene co-expression network of glaucoma‑related DEGs was constructed with 91 nodes. Furthermore, DEGs of TGF-β1 and -2 treated glaucoma in GO terms and pathways were inserted, and 29 common DEGs were identified. Based on these DEGs, gene co-expression network was constructed with 12 nodes and 16 edges. Finally, a total of 6 important DEGs of disease and treatment were inserted and obtained. They were HGF, AKR1B10, AKR1C3, PPAP2B, INHBA and BCAT1. The expression of HGF, AKR1B10 and AKR1C3 was decreased in glaucoma samples and treatment samples. In conclusion, HGF, AKR1B10 and AKR1C3 may be key genes for glaucoma diagnosis and treatment.

View Figures

View References

1	Martus P, Stroux A, Budde WM, Mardin CY, Korth M and Jonas JB: Predictive factors for progressive optic nerve damage in various types of chronic open-angle glaucoma. Am J Ophthalmol. 139:999–1009. 2005. View Article : Google Scholar : PubMed/NCBI
2	Graham SL, Butlin M, Lee M and Avolio AP: Central blood pressure, arterial waveform analysis, and vascular risk factors in glaucoma. J Glaucoma. 22:98–103. 2013. View Article : Google Scholar : PubMed/NCBI
3	Curriero FC, Pinchoff J, van Landingham SW, Ferrucci L, Friedman DS and Ramulu PY: Alteration of travel patterns with vision loss from glaucoma and macular degeneration. JAMA Ophthalmol. 131:1420–1426. 2013. View Article : Google Scholar : PubMed/NCBI
4	Skarie JM and Link BA: The primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway. Hum Mol Genet. 17:2474–2485. 2008. View Article : Google Scholar : PubMed/NCBI
5	Borrás T, Buie LK and Spiga MG: Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy. Gene Ther. 23:438–449. 2016. View Article : Google Scholar : PubMed/NCBI
6	Fan BJ and Wiggs JL: Glaucoma: Genes, phenotypes, and new directions for therapy. J Clin Invest. 120:3064–3072. 2010. View Article : Google Scholar : PubMed/NCBI
7	Jelodari-Mamaghani S, Haji-Seyed-Javadi R, Suri F, Nilforushan N, Yazdani S, Kamyab K and Elahi E: Contribution of the latent transforming growth factor-β binding protein 2 gene to etiology of primary open angle glaucoma and pseudoexfoliation syndrome. Mol Vis. 19:333–347. 2013.PubMed/NCBI
8	Kumar A, Basavaraj MG, Gupta SK, Qamar I, Ali AM, Bajaj V, Ramesh TK, Prakash DR, Shetty JS and Dorairaj SK: Role of CYP1B1, MYOC, OPTN, and OPTC genes in adult-onset primary open-angle glaucoma: Predominance of CYP1B1 mutations in Indian patients. Mol Vis. 13:667–676. 2007.PubMed/NCBI
9	Tanwar M, Kumar M, Dada T, Sihota R and Dada R: MYOC and FOXC1 gene analysis in primary congenital glaucoma. Mol Vis. 16:1996–2006. 2010.PubMed/NCBI
10	Kennedy KD, AnithaChristy SA, Buie LK and Borrás T: Cystatin a, a potential common link for mutant myocilin causative glaucoma. PLoS One. 7:e363012012. View Article : Google Scholar : PubMed/NCBI
11	Keller PJ, Arendt LM, Skibinski A, Logvinenko T, Klebba I, Dong S, Smith AE, Prat A, Perou CM, Gilmore H, et al: Defining the cellular precursors to human breast cancer. Proc Natl Acad Sci USA. 109:2772–2777. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zheng-Bradley X, Rung J, Parkinson H and Brazma A: Large scale comparison of global gene expression patterns in human and mouse. Genome Biol. 11:R1242010. View Article : Google Scholar : PubMed/NCBI
13	Grace C and Nacheva EP: Significance analysis of microarrays (SAM) offers clues to differences between the genomes of adult Philadelphia positive ALL and the lymphoid blast transformation of CML. Cancer Inform. 11:173–183. 2012. View Article : Google Scholar : PubMed/NCBI
14	Harris MA, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C, et al: The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 32:D258–D261. 2004. View Article : Google Scholar : PubMed/NCBI
15	Kechris KJ, Biehs B and Kornberg TB: Generalizing moving averages for tiling arrays using combined p-value statistics. Stat Appl Genet Mol Biol. 9:Article 29. 2010. View Article : Google Scholar : PubMed/NCBI
16	Tanabe M and Kanehisa M: Using the KEGG database resource. Curr Protoc Bioinformatics. 1:122012.PubMed/NCBI
17	Quigley HA: Glaucoma. Lancet. 377:1367–1377. 2011. View Article : Google Scholar : PubMed/NCBI
18	Baykal C, Demirtas E, Al A and Ayhan A, Yuce K, Tulunay G, Kose MF and Ayhan A: Comparison of HGF (hepatocyte growth factor) levels of epithelial ovarian cancer cyst fluids with benign ovarian cysts. Int J Gynecol Cancer. 13:771–775. 2003. View Article : Google Scholar : PubMed/NCBI
19	Engel LA, Muether PS, Fauser S and Hueber A: The effect of previous surgery and topical eye drops for primary open-angle glaucoma on cytokine expression in aqueous humor. Graefes Arch Clin Exp Ophthalmol. 252:791–799. 2014. View Article : Google Scholar : PubMed/NCBI
20	Awadalla MS, Thapa SS, Burdon KP, Hewitt AW and Craig JE: The association of hepatocyte growth factor (HGF) gene with primary angle closure glaucoma in the Nepalese population. Mol Vis. 17:2248–2254. 2011.PubMed/NCBI
21	Daniels JT, Limb GA, Saarialho-Kere U, Murphy G and Khaw PT: Human corneal epithelial cells require MMP-1 for HGF-mediated migration on collagen I. Invest Ophthalmol Vis Sci. 44:1048–1055. 2003. View Article : Google Scholar : PubMed/NCBI
22	Jiang YQ, Nagy RM and Spaeth GL: Effect of aqueous humor factors on the inhibition or enhancement of mitosis: An exploration of pathogenesis of primary open-angle glaucoma. Chin Med J (Engl). 98:833–834. 1985.PubMed/NCBI
23	Lewis MP, Lygoe KA, Nystrom ML, Anderson WP, Speight PM, Marshall JF and Thomas GJ: Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells. Br J Cancer. 90:822–832. 2004. View Article : Google Scholar : PubMed/NCBI
24	Lalive PH, Paglinawan R, Biollaz G, Kappos EA, Leone DP, Malipiero U, Relvas JB, Moransard M, Suter T and Fontana A: TGF-beta-treated microglia induce oligodendrocyte precursor cell chemotaxis through the HGF-c-Met pathway. Eur J Immunol. 35:727–737. 2005. View Article : Google Scholar : PubMed/NCBI
25	Tripathi RC, Li J, Chan WF and Tripathi BJ: Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res. 59:723–727. 1994. View Article : Google Scholar : PubMed/NCBI
26	Huang SP, Palla S, Ruzycki P, Varma RA, Harter T, Reddy GB and Petrash JM: Aldo-keto reductases in the eye. J Ophthalmol. 2010:5212042010. View Article : Google Scholar : PubMed/NCBI
27	Varma D, Sihota R and Agarwal HC: Evaluation of efficacy and safety of daunorubicin in glaucoma filtering surgery. Eye (Lond). 21:784–788. 2007. View Article : Google Scholar : PubMed/NCBI
28	Ren JM: Experimental study on doxorubicin as an adjunct to glaucoma surgery. Zhonghua Yan Ke Za Zhi. 25:351–354. 1989.(In Chinese). PubMed/NCBI
29	Tezel G: The immune response in glaucoma: A perspective on the roles of oxidative stress. Exp Eye Res. 93:178–186. 2011. View Article : Google Scholar : PubMed/NCBI
30	To CH, Kong CW, Chan CY, Shahidullah M and Do CW: The mechanism of aqueous humour formation. Clin Exp Optom. 85:335–349. 2002. View Article : Google Scholar : PubMed/NCBI
31	Wu C, Huang RT, Kuo CH, Kumar S, Kim CW, Lin YC, Chen YJ, Birukova A, Birukov KG, Dulin NO, et al: Mechanosensitive PPAP2B regulates endothelial responses to atherorelevant hemodynamic forces. Circ Res. 117:e41–e53. 2015. View Article : Google Scholar : PubMed/NCBI
32	Chiasseu M, Cueva Vargas JL, Destroismaisons L, Vande Velde C, Leclerc N and Di Polo A: Tau accumulation, altered phosphorylation, and missorting promote neurodegeneration in glaucoma. J Neurosci. 36:5785–5798. 2016. View Article : Google Scholar : PubMed/NCBI
33	Elisaf M, Kitsos G, Bairaktari E, Kalaitzidis R, Kalogeropoulos C and Psilas K: Metabolic abnormalities in patients with primary open-angle glaucoma. Acta Ophthalmol Scand. 79:129–132. 2001. View Article : Google Scholar : PubMed/NCBI