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CLC number: R737.25

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2020-02-03

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ji-li Wang

https://orcid.org/0000-0002-8976-508X

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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.3 P.246-255

http://doi.org/10.1631/jzus.B1900329


Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods#


Author(s):  Ji-li Wang, Yan Wang, Guo-ping Ren

Affiliation(s):  Department of Pathology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   gpren2002@163.com

Key Words:  Bioinformatics, Protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), Differentially expressed genes (DEGs), Castration-resistant prostate cancer (CRPC), Functional enrichment


Ji-li Wang, Yan Wang, Guo-ping Ren. Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods#[J]. Journal of Zhejiang University Science B, 2020, 21(3): 246-255.

@article{title="Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods#",
author="Ji-li Wang, Yan Wang, Guo-ping Ren",
journal="Journal of Zhejiang University Science B",
volume="21",
number="3",
pages="246-255",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900329"
}

%0 Journal Article
%T Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods#
%A Ji-li Wang
%A Yan Wang
%A Guo-ping Ren
%J Journal of Zhejiang University SCIENCE B
%V 21
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%P 246-255
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900329

TY - JOUR
T1 - Identification of PTPRR and JAG1 as key genes in castration-resistant prostate cancer by integrated bioinformatics methods#
A1 - Ji-li Wang
A1 - Yan Wang
A1 - Guo-ping Ren
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 3
SP - 246
EP - 255
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900329


Abstract: 
To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein–protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.

通过生物信息学方法鉴定PTPRR和JAG1为去势抵抗性前列腺癌(CRPC)的关键基因

目的:鉴定去势抵抗性前列腺癌(CRPC)的关键基因.
创新点:(1)结合多个数据库数据,运用生物信息学方法鉴定CRPC的关键基因;(2)首次报道PTPRR可能在CRPC里起关键作用.
方法:通过下载三个GEO数据库的mRNA微阵列数据,分析CRPC和激素敏感前列腺癌之间的基因差异,对筛选出的差异基因进行功能富集分析和蛋白质间相互作用分析,最终筛选出两个有重要功能的差异基因(PTPRRJAG1).通过在多个其他数据库中进行表达量验证和生存分析,进一步证明这些基因的重要作用.
结论:PTPRRJAG1在CRPC中显著增高,并与预后差相关.因此,这两个基因有可能作为CRPC的诊断和预后的生物标志物.

关键词:生物信息学;PTPRR;JAG1;差异表达基因;激素抵抗前列腺癌;功能富集

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Artavanis-Tsakonas S, Rand MD, Lake RJ, 1999. Notch signaling: cell fate control and signal integration in development. Science, 284(5415):770-776.

[2]Attard G, Parker C, Eeles RA, et al., 2016. Prostate cancer. Lancet, 387(10013):70-82.

[3]Chang CC, Huang RL, Wang HC, et al., 2014. High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma. Int J Gynecol Cancer, 24(2):201-209.

[4]Chen WQ, Zheng RS, Baade PD, et al., 2016. Cancer statistics in China, 2015. CA Cancer J Clin, 66(2):115-132.

[5]D'Antonio JM, Ma CQ, Monzon FA, et al., 2008. Longitudinal analysis of androgen deprivation of prostate cancer cells identifies pathways to androgen independence. Prostate, 68(7):698-714.

[6]Dennis G Jr, Sherman BT, Hosack DA, et al., 2003. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol, 4(5):P3.

[7]Duś-Szachniewicz K, Woźniak M, Nelke K, et al., 2015. Protein tyrosine phosphatase receptor R and Z1 expression as independent prognostic indicators in oral squamous cell carcinoma. Head Neck, 37(12):1816-1822.

[8]Espinoza I, Pochampally R, Xing F, et al., 2013. Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Ther, 6:1249-1259.

[9]Gautier L, Cope L, Bolstad BM, et al., 2004. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics, 20(3):307-315.

[10]Gene Ontology Consortium, 2004. The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res, 32(S1):D258-D261.

[11]Guo YZ, Sun HH, Wang XT, et al., 2018. Transcriptomic analysis reveals key lncRNAs associated with ribosomal biogenesis and epidermis differentiation in head and neck squamous cell carcinoma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(9):674-688.

[12]Heidenreich A, Bastian PJ, Bellmunt J, et al., 2014. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol, 65(2):467-479.

[13]Kanehisa M, Goto S, 2000. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res, 28(1):27-30.

[14]Kwon OJ, Zhang L, Wang JH, et al., 2016. Notch promotes tumor metastasis in a prostate-specific Pten-null mouse model. J Clin Invest, 126(7):2626-2641.

[15]Laczmanska I, Karpinski P, Bebenek M, et al., 2013. Protein tyrosine phosphatase receptor-like genes are frequently hypermethylated in sporadic colorectal cancer. J Hum Genet, 58(1):11-15.

[16]Li DM, Masiero M, Banham AH, et al., 2014. The Notch ligand Jagged1 as a target for anti-tumor therapy. Front Oncol, 4:254.

[17]Lin Y, Shen Z, Song X, et al., 2018. Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(12):895-909.

[18]Logothetis CJ, Lin SH, 2005. Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer, 5(1):21-28.

[19]Menigatti M, Cattaneo E, Sabates-Bellver J, et al., 2009. The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis. Mol Cancer, 8:124.

[20]Munkley J, Lafferty NP, Kalna G, et al., 2015. Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells. BMC Cancer, 15:9.

[21]Noordman YE, Jansen PAM, Hendriks WJAJ, 2006. Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells. J Mol Signal, 1:4.

[22]Ritchie ME, Phipson B, Wu D, et al., 2015. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 43(7):e47.

[23]Santagata S, Demichelis F, Riva A, et al., 2004. JAGGED1 expression is associated with prostate cancer metastasis and recurrence. Cancer Res, 64(19):6854-6857.

[24]Schmitt I, Bitoun E, Manto M, 2009. PTPRR, cerebellum, and motor coordination. Cerebellum, 8(2):71-73.

[25]Sethi N, Dai XD, Winter CG, et al., 2011. Tumor-derived Jagged1 promotes osteolytic bone metastasis of breast cancer by engaging Notch signaling in bone cells. Cancer Cell, 19(2):192-205.

[26]Shannon P, Markiel A, Ozier O, et al., 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 13(11):2498-2504.

[27]Shou JY, Ross S, Koeppen H, et al., 2001. Dynamics of Notch expression during murine prostate development and tumorigenesis. Cancer Res, 61(19):7291-7297.

[28]Siegel RL, Miller KD, Jemal A, 2019. Cancer statistics, 2019. CA Cancer J Clin, 69(1):7-34.

[29]Su L, Song X, Xue Z, et al., 2018. Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(4):293-304.

[30]Su PH, Lin YW, Huang RL, et al., 2013. Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer. Oncogene, 32(1):15-26.

[31]Su Q, Zhang B, Zhang L, et al., 2017. Jagged1 upregulation in prostate epithelial cells promotes formation of reactive stroma in the Pten null mouse model for prostate cancer. Oncogene, 36(5):618-627.

[32]Sun YT, Wang BE, Leong KG, et al., 2012. Androgen deprivation causes epithelial-mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Res, 72(2):527-536.

[33]Szklarczyk D, Morris JH, Cook H, et al., 2017. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res, 45(D1):D362-D368.

[34]Tang ZF, Li CW, Kang BX, et al., 2017. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res, 45(W1):W98-W102.

[35]Terada N, Shimizu Y, Kamba T, et al., 2010. Identification of EP4 as a potential target for the treatment of castration-resistant prostate cancer using a novel xenograft model. Cancer Res, 70(4):1606-1615.

[36]Watson PA, Arora VK, Sawyers CL, 2015. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer, 15(12):701-711.

[37]Weinstein JN, Collisson EA, Mills GB, et al., 2013. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet, 45(10):1113-1120.

[38]Woźniak M, Gamian E, Łaczmańska I, et al., 2014. Immunohistochemical and Western blot analysis of two protein tyrosine phosphatase receptors, R and Z1, in colorectal carcinoma, colon adenoma and normal colon tissues. Histol Histopathol, 29(5):635-639.

[39]Yong T, Sun A, Henry MD, et al., 2011. Down regulation of CSL activity inhibits cell proliferation in prostate and breast cancer cells. J Cell Biochem, 112(9):2340-2351.

[40]Zhu H, Zhou XC, Redfield S, et al., 2013. Elevated Jagged-1 and Notch-1 expression in high grade and metastatic prostate cancers. Am J Transl Res, 5(3):368-378.

[41]Zhu H, Li Y, Wang M, et al., 2019. Analysis of cardiovascular disease-related NF-κB-regulated genes and microRNAs in TNFα-treated primary mouse vascular endothelial cells. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(10):803-815.

[42]List of electronic supplementary materials

[43]Table S1 Clinical characteristics of samples in this study

[44]Fig. S1 Expression of the PTPRR in Grasso PCa

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