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Open Access 01-12-2021 | Nephroblastoma | Research article

Identification of the potential novel biomarkers as susceptibility gene for Wilms tumor

Authors: Li Liu, Zhe Song, Xu-Dong Gao, Xian Chen, Xiao-Bin Wu, Mi Wang, Yu-De Hong

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Wilms tumor (WT) is the most common malignant renal tumor in children. The aim of this study was to identify potential susceptibility gene of WT for better prognosis.

Methods

Weighted gene coexpression network analysis is used for the detection of clinically important biomarkers associated with WT.

Results

In the study, 59 tissue samples from National Cancer Institute were pretreated for constructing gene co-expression network, while 224 samples also downloaded from National Cancer Institute were used for hub gene validation and module preservation analysis. Three modules were found to be highly correlated with WT, and 44 top hub genes were identified in these key modules eventually. In addition, both the module preservation analysis and gene validation showed ideal results based on other dataset with 224 samples. Meanwhile, Functional enrichment analysis showed that genes in module were enriched to sister chromatid cohesion, cell cycle, oocyte meiosis.

Conclusion

In summary, we established a gene co-expression network to identify 44 hub genes are closely to recurrence and staging of WT, and 6 of these hub genes was closely related to the poor prognosis of patients. Our findings revealed that those hub genes may be used as potential susceptibility gene for clinical diagnosis and prognosis of this tumor.

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Phelps HM, Kaviany S, Borinstein SC, Lovvorn HN 3rd. Biological drivers of Wilms tumor prognosis and treatment. Children (Basel). 2018;5:145.

Treger TD, Chowdhury T, Pritchard-Jones K, Behjati S. The genetic changes of Wilms tumour. Nat Rev Nephrol. 2019;15(4):240–51. https://doi.org/10.1038/s41581-019-0112-0.CrossRefPubMed

Dix DB, Fernandez CV, Chi YY, Mullen EA, Geller JI, Gratias EJ, et al. Augmentation of therapy for combined loss of Heterozygosity 1p and 16q in favorable histology Wilms tumor: a Children's oncology group AREN0532 and AREN0533 study report. J Clin Oncol. 2019;37(30):2769–77. https://doi.org/10.1200/JCO.18.01972.CrossRefPubMedPubMedCentral

Fernandez CV, Perlman EJ, Mullen EA, Chi YY, Hamilton TE, Gow KW, et al. Clinical outcome and biological predictors of relapse after nephrectomy only for very low-risk Wilms tumor: a report from Children's oncology group AREN0532. Ann Surg. 2017;265(4):835–40. https://doi.org/10.1097/SLA.0000000000001716.CrossRefPubMed

Holl EK, Routh JC, Johnston AW, Frazier V, Rice HE, Tracy ET, et al. Immune expression in children with Wilms tumor: a pilot study. J Pediatr Urol. 2019;15:441.e1-.e8.CrossRef

Spreafico F, Pritchard Jones K, Malogolowkin MH, Bergeron C, Hale J, de Kraker J, et al. Treatment of relapsed Wilms tumors: lessons learned. Expert Rev Anticancer Ther. 2009;9(12):1807–15. https://doi.org/10.1586/era.09.159.CrossRefPubMed

Malogolowkin M, Cotton CA, Green DM, Breslow NE, Perlman E, Miser J, et al. Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer. 2008;50(2):236–41. https://doi.org/10.1002/pbc.21267.CrossRefPubMed

Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9(1):559. https://doi.org/10.1186/1471-2105-9-559.CrossRefPubMedPubMedCentral

Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249–64. https://doi.org/10.1093/biostatistics/4.2.249.CrossRefPubMed

10.

Zhao W, Langfelder P, Fuller T, Dong J, Li A, Hovarth S. Weighted gene coexpression network analysis: state of the art. J Biopharm Stat. 2010;20(2):281–300. https://doi.org/10.1080/10543400903572753.CrossRefPubMed

11.

Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. 2005;4:Article17.CrossRefPubMed

12.

Langfelder P, Luo R, Oldham MC, Horvath S. Is my network module preserved and reproducible? PLoS Comput Biol. 2011;7(1):e1001057. https://doi.org/10.1371/journal.pcbi.1001057.CrossRefPubMedPubMedCentral

13.

Guo SM, Wang JX, Li J, Xu FY, Wei Q, Wang HM, et al. Identification of gene expression profiles and key genes in subchondral bone of osteoarthritis using weighted gene coexpression network analysis. J Cell Biochem. 2018;119(9):7687–95. https://doi.org/10.1002/jcb.27118.CrossRefPubMed

14.

Jeong H, Mason SP, Barabasi AL, Oltvai ZN. Lethality and centrality in protein networks. Nature. 2001;411(6833):41–2. https://doi.org/10.1038/35075138.CrossRefPubMed

15.

Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(W1):W90–7. https://doi.org/10.1093/nar/gkw377.CrossRefPubMedPubMedCentral

16.

Goel MK, Khanna P, Kishore J. Understanding survival analysis: Kaplan-Meier estimate. Int J Ayurveda Res. 2010;1(4):274–8. https://doi.org/10.4103/0974-7788.76794.CrossRefPubMedPubMedCentral

17.

Brok J, Treger TD, Gooskens SL, van den Heuvel-Eibrink MM, Pritchard-Jones K. Biology and treatment of renal tumours in childhood. Eur J Cancer. 2016;68:179–95. https://doi.org/10.1016/j.ejca.2016.09.005.CrossRefPubMed

18.

Wittmann S, Zirn B, Alkassar M, Ambros P, Graf N, Gessler M. Loss of 11q and 16q in Wilms tumors is associated with anaplasia, tumor recurrence, and poor prognosis. Genes Chromosomes Cancer. 2007;46(2):163–70. https://doi.org/10.1002/gcc.20397.CrossRefPubMed

19.

Grundy RG, Pritchard J, Scambler P, Cowell JK. Loss of heterozygosity on chromosome 16 in sporadic Wilms' tumour. Br J Cancer. 1998;78(9):1181–7. https://doi.org/10.1038/bjc.1998.651.CrossRefPubMedPubMedCentral

20.

Spreafico F, Gamba B, Mariani L, Collini P, D'Angelo P, Pession A, et al. Loss of heterozygosity analysis at different chromosome regions in Wilms tumor confirms 1p allelic loss as a marker of worse prognosis: a study from the Italian Association of Pediatric Hematology and Oncology. J Urol. 2013;189(1):260–6. https://doi.org/10.1016/j.juro.2012.09.009.CrossRefPubMed

21.

Kim JS, He X, Liu J, Duan Z, Kim T, Gerard J, et al. Systematic proteomics of endogenous human cohesin reveals an interaction with diverse splicing factors and RNA binding proteins required for mitotic progression. J Biol Chem. 2019;294(22):8760–72. https://doi.org/10.1074/jbc.RA119.007832.CrossRefPubMedPubMedCentral

22.

Repo H, Loyttyniemi E, Nykanen M, Lintunen M, Karra H, Pitkanen R, et al. The expression of Cohesin subunit SA2 predicts breast cancer survival. Appl Immunohistochem Mol Morphol. 2016;24(9):615–21. https://doi.org/10.1097/PAI.0000000000000240.CrossRefPubMed

23.

Mintzas K, Heuser M. Emerging strategies to target the dysfunctional cohesin complex in cancer. Expert Opin Ther Targets. 2019;23(6):525–37.

24.

Mizukami T, Izawa N, Nakajima TE, Sunakawa Y. Targeting EGFR and RAS/RAF signaling in the treatment of metastatic colorectal cancer: from current treatment strategies to future perspectives. Drugs. 2019;79(6):633–45. https://doi.org/10.1007/s40265-019-01113-0.CrossRefPubMed

25.

Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, et al. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009;8(2):324–32. https://doi.org/10.1158/1535-7163.MCT-08-0890.CrossRefPubMed

26.

Xi C, Wang L, Yu J, Ye H, Cao L, Gong Z. Inhibition of cyclin-dependent kinases by AT7519 is effective to overcome chemoresistance in colon and cervical cancer. Biochem Biophys Res Commun. 2019;513(3):589–93. https://doi.org/10.1016/j.bbrc.2019.04.014.CrossRefPubMed

27.

Du M, Qiu Q, Gruslin A, Gordon J, He M, Chan CC, et al. SB225002 promotes mitotic catastrophe in chemo-sensitive and -resistant ovarian cancer cells independent of p53 status in vitro. PLoS One. 2013;8(1):e54572. https://doi.org/10.1371/journal.pone.0054572.CrossRefPubMedPubMedCentral

28.

Hung KC, Wang SG, Lin ML, Chen SS. Citrate-induced p85alpha(−)PTEN complex formation causes G2/M phase arrest in human pharyngeal squamous carcinoma cell lines. Int J Mol Sci. 2019;20(9). https://doi.org/10.3390/ijms20092105.

29.

Makarevic J, Rutz J, Juengel E, Maxeiner S, Tsaur I, Chun FK, et al. Influence of the HDAC inhibitor Valproic acid on the growth and proliferation of Temsirolimus-resistant prostate cancer cells in vitro. Cancers (Basel). 2019;11(4):566.

30.

Liu J, Li S, Liang J, Jiang Y, Wan Y, Zhou S, et al. ITLNI identified by comprehensive bioinformatic analysis as a hub candidate biological target in human epithelial ovarian cancer. Cancer Manag Res. 2019;11:2379–92. https://doi.org/10.2147/CMAR.S189784.CrossRefPubMedPubMedCentral

31.

Mohanta S, Sekhar Khora S, Suresh A. Cancer stem cell based molecular predictors of tumor recurrence in Oral squamous cell carcinoma. Arch Oral Biol. 2019;99:92–106. https://doi.org/10.1016/j.archoralbio.2019.01.002.CrossRefPubMed

32.

Piao J, Zhu L, Sun J, Li N, Dong B, Yang Y, et al. High expression of CDK1 and BUB1 predicts poor prognosis of pancreatic ductal adenocarcinoma. Gene. 2019;701:15–22. https://doi.org/10.1016/j.gene.2019.02.081.CrossRefPubMed

33.

Halliday BJ, Fukuzawa R, Markie DM, Grundy RG, Ludgate JL, Black MA, et al. Germline mutations and somatic inactivation of TRIM28 in Wilms tumour. PLoS Genet. 2018;14(6):e1007399. https://doi.org/10.1371/journal.pgen.1007399.CrossRefPubMedPubMedCentral

34.

Mahamdallie S, Yost S, Poyastro-Pearson E, Holt E, Zachariou A, Seal S, et al. Identification of new Wilms tumour predisposition genes: an exome sequencing study. Lancet Child Adolesc Health. 2019;3(5):322–31. https://doi.org/10.1016/S2352-4642(19)30018-5.CrossRefPubMedPubMedCentral

35.

Diets IJ, Hoyer J, Ekici AB, Popp B, Hoogerbrugge N, van Reijmersdal SV, et al. TRIM28 haploinsufficiency predisposes to Wilms tumor. Int J Cancer. 2019;145(4):941–51. https://doi.org/10.1002/ijc.32167.CrossRefPubMed

36.

Hou T, Lou Y, Li S, Zhao C, Ji Y, Wang D, et al. Kadsurenone is a useful and promising treatment strategy for breast cancer bone metastases by blocking the PAF/PTAFR signaling pathway. Oncol Lett. 2018;16(2):2255–62. https://doi.org/10.3892/ol.2018.8935.CrossRefPubMedPubMedCentral

37.

Chase PB, Yang JM, Thompson FH, Halonen M, Regan JW. Regional mapping of the human platelet-activating factor receptor gene (PTAFR) to 1p35-->p34.3 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1996;72(2-3):205–7. https://doi.org/10.1159/000134190.CrossRefPubMed

38.

Liu L, Chen F, Xiu A, Du B, Ai H, Xie W. Identification of key candidate genes and pathways in endometrial cancer by integrated Bioinformatical analysis. Asian Pac J Cancer Prev. 2018;19(4):969–75. https://doi.org/10.22034/APJCP.2018.19.4.969.CrossRefPubMedPubMedCentral

39.

Wang X, Song P, Huang C, Yuan N, Zhao X, Xu C. Weighted gene coexpression network analysis for identifying hub genes in association with prognosis in Wilms tumor. Mol Med Rep. 2019;19(3):2041–50. https://doi.org/10.3892/mmr.2019.9881.CrossRefPubMedPubMedCentral

40.

Jiang X, Li H. MiR-1180-5p regulates apoptosis of Wilms' tumor by targeting p73. Onco Targets Ther. 2018;11:823–31. https://doi.org/10.2147/OTT.S148684.CrossRefPubMedPubMedCentral

41.

de Sa Pereira BM, Montalvao-de-Azevedo R, Faria PA, de Paula SN, Nicolau-Neto P, Maschietto M, et al. Association between long interspersed nuclear element-1 methylation levels and relapse in Wilms tumors. Clin Epigenetics. 2017;9(1):128. https://doi.org/10.1186/s13148-017-0431-6.CrossRefPubMedPubMedCentral

42.

Shimizu Y, Suzuki T, Yoshikawa T, Endo I, Nakatsura T. Next-generation cancer immunotherapy targeting Glypican-3. Front Oncol. 2019;9:248. https://doi.org/10.3389/fonc.2019.00248.CrossRefPubMedPubMedCentral

43.

Chen W, Zhuang J, Gong L, Dai Y, Diao H. Investigating the dysfunctional pathogenesis of Wilms' tumor through a multidimensional integration strategy. Ann Transl Med. 2019;7(7):136. https://doi.org/10.21037/atm.2019.03.37.CrossRefPubMedPubMedCentral

Title: Identification of the potential novel biomarkers as susceptibility gene for Wilms tumor
Authors: Li Liu
Zhe Song
Xu-Dong Gao
Xian Chen
Xiao-Bin Wu
Mi Wang
Yu-De Hong
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Nephroblastoma
Biomarkers
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08034-w

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Abstract

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Methods

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