Identification of Biomarkers Correlated with the TNM Staging and Overall Survival of Patients with Bladder Cancer

Overview

Journal Front Physiol

Date 2017 Dec 14

PMID 29234286

Citations 63

Authors

Sheng Li

Xiaoping Liu

Tongzu Liu

XiangYu Meng

Xiaohong Yin

Cheng Fang

Di Huang

Yue Cao

Hong Weng

Xiantao Zeng

Xinghuan Wang

Affiliations

Soon will be listed here.

Abstract

To identify candidate biomarkers correlated with clinical prognosis of patients with bladder cancer (BC). Weighted gene co-expression network analysis was applied to build a co-expression network to identify hub genes correlated with tumor node metastasis (TNM) staging of BC patients. Functional enrichment analysis was conducted to functionally annotate the hub genes. Protein-protein interaction network analysis of hub genes was performed to identify the interactions among the hub genes. Survival analyses were conducted to characterize the role of hub genes on the survival of BC patients. Gene set enrichment analyses were conducted to find the potential mechanisms involved in the tumor proliferation promoted by hub genes. Based on the results of topological overlap measure based clustering and the inclusion criteria, top 50 hub genes were identified. Hub genes were enriched in cell proliferation associated gene ontology terms (mitotic sister chromatid segregation, mitotic cell cycle and, cell cycle, etc.) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (cell cycle, Oocyte meiosis, etc.). 17 hub genes were found to interact with ≥5 of the hub genes. Survival analysis of hub genes suggested that lower expression of MMP11, COL5A2, CDC25B, TOP2A, CENPF, CDCA3, TK1, TPX2, CDCA8, AEBP1, and FOXM1were associated with better overall survival of BC patients. BC samples with higher expression of hub genes were enriched in gene sets associated with P53 pathway, apical junction, mitotic spindle, G2M checkpoint, and myogenesis, etc. We identified several candidate biomarkers correlated with the TNM staging and overall survival of BC patients. Accordingly, they might be used as potential diagnostic biomarkers and therapeutic targets with clinical utility.

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References

Riester M, Taylor J, Feifer A, Koppie T, Rosenberg J, Downey R . Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer. Clin Cancer Res. 2012; 18(5):1323-33. PMC: 3569085. DOI: 10.1158/1078-0432.CCR-11-2271. View

Uchida F, Uzawa K, Kasamatsu A, Takatori H, Sakamoto Y, Ogawara K . Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest. BMC Cancer. 2012; 12:321. PMC: 3418557. DOI: 10.1186/1471-2407-12-321. View

Yaxley J . Urinary tract cancers: An overview for general practice. J Family Med Prim Care. 2017; 5(3):533-538. PMC: 5290755. DOI: 10.4103/2249-4863.197258. View

Yau C, Meyer L, Benz S, Vaske C, Scott G, Egan B . FOXM1 cistrome predicts breast cancer metastatic outcome better than FOXM1 expression levels or tumor proliferation index. Breast Cancer Res Treat. 2015; 154(1):23-32. DOI: 10.1007/s10549-015-3589-7. View

Wang M, Zhu X, Wang L, Lin Y . Expression and significance of CDC25B, PED/PEA-15 in esophageal carcinoma. Cancer Biother Radiopharm. 2015; 30(3):139-45. DOI: 10.1089/cbr.2014.1701. View

Zhang B, Horvath S . A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. 2006; 4:Article17. DOI: 10.2202/1544-6115.1128. View

Langfelder P, Horvath S . WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008; 9:559. PMC: 2631488. DOI: 10.1186/1471-2105-9-559. View

Tarpgaard L, Qvortrup C, Nygard S, Nielsen S, Andersen D, Jensen N . A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification. BMC Cancer. 2016; 16:91. PMC: 4750171. DOI: 10.1186/s12885-016-2124-5. View

Deng H, Guo R, Li W, Zhao M, Lu Y . Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells. Biochem Biophys Res Commun. 2004; 326(2):274-81. DOI: 10.1016/j.bbrc.2004.11.027. View

10.

Yan G, Zou F, Dang B, Zhang Y, Yu G, Liu X . Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study. Proteomics. 2012; 12(14):2391-9. DOI: 10.1002/pmic.201100652. View

11.

Wang T, Liu Z, Shi F, Wang J . Pin1 modulates chemo-resistance by up-regulating FoxM1 and the involvements of Wnt/β-catenin signaling pathway in cervical cancer. Mol Cell Biochem. 2016; 413(1-2):179-87. DOI: 10.1007/s11010-015-2651-4. View

12.

Tomii C, Inokuchi M, Takagi Y, Ishikawa T, Otsuki S, Uetake H . TPX2 expression is associated with poor survival in gastric cancer. World J Surg Oncol. 2017; 15(1):14. PMC: 5223319. DOI: 10.1186/s12957-016-1095-y. View

13.

Hu W, Jin L, Jiang C, Long G, Scolyer R, Wu Q . AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma. Cell Death Dis. 2013; 4:e914. PMC: 3847319. DOI: 10.1038/cddis.2013.441. View

14.

Mohammed A, El-Tanni H, El-Khatib H, Mirza A, Mirza A, Alturaifi T . Urinary Bladder Cancer: Biomarkers and Target Therapy, New Era for More Attention. Oncol Rev. 2017; 10(2):320. PMC: 5178843. DOI: 10.4081/oncol.2016.320. View

15.

Pang L, Wang D, Zhang N, Xu D, Meng X . Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients. Cancer Biomark. 2016; 16(4):599-607. DOI: 10.3233/CBM-160601. View

16.

Li L, Fan B, Zhang L, Xing X, Cheng X, Wang X . Trichostatin A potentiates TRAIL-induced antitumor effects via inhibition of ERK/FOXM1 pathway in gastric cancer. Tumour Biol. 2016; 37(8):10269-78. DOI: 10.1007/s13277-016-4816-5. View

17.

Kamat A, Hahn N, Efstathiou J, Lerner S, Malmstrom P, Choi W . Bladder cancer. Lancet. 2016; 388(10061):2796-2810. DOI: 10.1016/S0140-6736(16)30512-8. View

18.

Yang Y, Li D, Shen N, Yu X, Li J, Song Q . TPX2 promotes migration and invasion of human breast cancer cells. Asian Pac J Trop Med. 2015; 8(12):1064-1070. DOI: 10.1016/j.apjtm.2015.11.007. View

19.

Wang J, Duncan D, Shi Z, Zhang B . WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013; 41(Web Server issue):W77-83. PMC: 3692109. DOI: 10.1093/nar/gkt439. View

20.

Yip A, Horvath S . Gene network interconnectedness and the generalized topological overlap measure. BMC Bioinformatics. 2007; 8:22. PMC: 1797055. DOI: 10.1186/1471-2105-8-22. View