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Erschienen in: Pathology & Oncology Research 3/2020

05.09.2019 | Original Article

Bioinformatics Analysis Suggests the Combined Expression of AURKB and KIF18B Being an Important Event in the Development of Clear Cell Renal Cell Carcinoma

verfasst von: Qianqian Liu, Xiling Zhang, Haichao Tang, Jinwei Liu, Chen Fu, Mingli Sun, Lin Zhao, Minjie Wei, Zhaojin Yu, Ping Wang

Erschienen in: Pathology & Oncology Research | Ausgabe 3/2020

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Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma with high metastatic rate and high mortality rate, needing to find potential therapeutic targets and develop new therapy methods. The bioinformatics analysis was used in this study to find the targets. Firstly, the expression profile of ccRCC obtained from The Cancer Genome Atlas (TCGA) database and GSE53757 dataset were used to identify the significant up-regulated genes. IL20RB, AURKB and KIF18B with the top efficiency of capable of diagnosis ccRCC from para cancer tissue, were over-expressed in ccRCC samples, and expressed increasedly with the development of ccRCC. There was the closest correlation between AURKB and KIF18B in these three over-expressed genes. AURKB (high) or KIF18B (high) were all significantly correlated with higher T, N, M stage, G grade and shorter overall survival (OS) of ccRCC patients. Furthermore, the ccRCC patients with AURKB (high) + KIF18B (high) showed worse clinical characteristics and prognosis. Multivariate COX regression analysis indicated AURKB (high) and KIF18B (high) were all the independent prognostic risk factor without considering the interaction of AURKB and KIF18B. Moreover, considering the combination of each other, only AURKB (high) + KIF18B (high) expression was an independent prognostic risk factor for ccRCC patients, but not other situations. Collectively, AURKB was closely associated with KIF18B, and the combined expression of AURKB and KIF18B may be of great significance in ccRCC.
Literatur
1.
Zurück zum Zitat Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424PubMed Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424PubMed
2.
Zurück zum Zitat Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L et al (2017) Renal cell carcinoma. Nat Rev Dis Primers 3(17009):9 Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L et al (2017) Renal cell carcinoma. Nat Rev Dis Primers 3(17009):9
3.
Zurück zum Zitat Hsieh JJ, Le V, Cao D, Cheng EH, Creighton CJ (2018) Genomic classifications of renal cell carcinoma: a critical step towards the future application of personalized kidney cancer care with pan-omics precision. J Pathol 244(5):525–537CrossRefPubMed Hsieh JJ, Le V, Cao D, Cheng EH, Creighton CJ (2018) Genomic classifications of renal cell carcinoma: a critical step towards the future application of personalized kidney cancer care with pan-omics precision. J Pathol 244(5):525–537CrossRefPubMed
4.
Zurück zum Zitat Li QK, Pavlovich CP, Zhang H, Kinsinger CR, Chan DW (2019) Challenges and opportunities in the proteomic characterization of clear cell renal cell carcinoma (ccRCC): a critical step towards the personalized care of renal cancers. Semin Cancer Biol 55:8–15CrossRefPubMed Li QK, Pavlovich CP, Zhang H, Kinsinger CR, Chan DW (2019) Challenges and opportunities in the proteomic characterization of clear cell renal cell carcinoma (ccRCC): a critical step towards the personalized care of renal cancers. Semin Cancer Biol 55:8–15CrossRefPubMed
6.
Zurück zum Zitat Keefe SM, Nathanson KL, Rathmell WK (2013) The molecular biology of renal cell carcinoma. Semin Oncol 40(4):421–428CrossRefPubMed Keefe SM, Nathanson KL, Rathmell WK (2013) The molecular biology of renal cell carcinoma. Semin Oncol 40(4):421–428CrossRefPubMed
7.
Zurück zum Zitat Fan Y, Ma X, Li H, Gao Y, Huang Q, Zhang Y, Bao X, du Q, Luo G, Liu K, Meng Q, Zhao C, Zhang X (2018) miR-122 promotes metastasis of clear-cell renal cell carcinoma by downregulating dicer. Int J Cancer 142(3):547–560CrossRefPubMed Fan Y, Ma X, Li H, Gao Y, Huang Q, Zhang Y, Bao X, du Q, Luo G, Liu K, Meng Q, Zhao C, Zhang X (2018) miR-122 promotes metastasis of clear-cell renal cell carcinoma by downregulating dicer. Int J Cancer 142(3):547–560CrossRefPubMed
8.
Zurück zum Zitat Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR et al (2013) The cancer genome atlas Pan-Cancer analysis project. Nat Genet 45(10):1113–1120CrossRef Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR et al (2013) The cancer genome atlas Pan-Cancer analysis project. Nat Genet 45(10):1113–1120CrossRef
9.
Zurück zum Zitat Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF et al (2013) NCBI GEO: archive for functional genomics datasets-update. Nucleic Acids Res 41:D991–D995CrossRefPubMed Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF et al (2013) NCBI GEO: archive for functional genomics datasets-update. Nucleic Acids Res 41:D991–D995CrossRefPubMed
10.
Zurück zum Zitat Wang Z, Yang B, Zhang M, Guo W, Wu Z et al (2018) lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell 33(4):706–720CrossRefPubMedPubMedCentral Wang Z, Yang B, Zhang M, Guo W, Wu Z et al (2018) lncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell 33(4):706–720CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Li B, Wang W, Li Z, Chen Z, Zhi X, Xu J, Li Q, Wang L, Huang X, Wang L, Wei S, Sun G, Zhang X, He Z, Zhang L, Zhang D, Xu H, el-Rifai W, Xu Z (2017) MicroRNA-148a-3p enhances cisplatin cytotoxicity in gastric cancer through mitochondrial fission induction and cyto-protective autophagy suppression. Cancer Lett 410:212–227CrossRefPubMedPubMedCentral Li B, Wang W, Li Z, Chen Z, Zhi X, Xu J, Li Q, Wang L, Huang X, Wang L, Wei S, Sun G, Zhang X, He Z, Zhang L, Zhang D, Xu H, el-Rifai W, Xu Z (2017) MicroRNA-148a-3p enhances cisplatin cytotoxicity in gastric cancer through mitochondrial fission induction and cyto-protective autophagy suppression. Cancer Lett 410:212–227CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Chen L, Yuan L, Qian K, Qian G, Zhu Y, Wu CL, Dan HC, Xiao Y, Wang X (2018) Identification of biomarkers associated with pathological stage and prognosis of clear cell renal cell carcinoma by co-expression network analysis. Front Physiol 9:399CrossRefPubMedPubMedCentral Chen L, Yuan L, Qian K, Qian G, Zhu Y, Wu CL, Dan HC, Xiao Y, Wang X (2018) Identification of biomarkers associated with pathological stage and prognosis of clear cell renal cell carcinoma by co-expression network analysis. Front Physiol 9:399CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Song J, Peng J, Zhu C, Bai G, Liu Y, Zhu J, Liu J (2018) Identification and validation of two novel prognostic lncRNAs in kidney renal clear cell carcinoma. Cell Physiol Biochem 48(6):2549–2562CrossRefPubMed Song J, Peng J, Zhu C, Bai G, Liu Y, Zhu J, Liu J (2018) Identification and validation of two novel prognostic lncRNAs in kidney renal clear cell carcinoma. Cell Physiol Biochem 48(6):2549–2562CrossRefPubMed
14.
Zurück zum Zitat Atkins MB, Tannir NM (2018) Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treat Rev 70:127–137CrossRefPubMed Atkins MB, Tannir NM (2018) Current and emerging therapies for first-line treatment of metastatic clear cell renal cell carcinoma. Cancer Treat Rev 70:127–137CrossRefPubMed
15.
Zurück zum Zitat Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, Martignoni G, Rini BI, Kutikov A (2015) Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol 67(1):85–97CrossRefPubMed Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, Martignoni G, Rini BI, Kutikov A (2015) Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol 67(1):85–97CrossRefPubMed
16.
Zurück zum Zitat Yan M, Wang C, He B, Yang M, Tong M et al (2016) Aurora-a kinase: a potent oncogene and target for cancer therapy. Med Res Rev 36(6):1036–1079CrossRefPubMed Yan M, Wang C, He B, Yang M, Tong M et al (2016) Aurora-a kinase: a potent oncogene and target for cancer therapy. Med Res Rev 36(6):1036–1079CrossRefPubMed
17.
Zurück zum Zitat Al-Khafaji AS, Davies MP, Risk JM, Marcus MW, Koffa M et al (2017) Aurora B expression modulates paclitaxel response in non-small cell lung cancer. Br J Cancer 116(5):592–599CrossRefPubMedPubMedCentral Al-Khafaji AS, Davies MP, Risk JM, Marcus MW, Koffa M et al (2017) Aurora B expression modulates paclitaxel response in non-small cell lung cancer. Br J Cancer 116(5):592–599CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Enjoji M, Iida S, Sugita H, Ishikawa T, Uetake H et al (2009) BubR1 and AURKB overexpression are associated with a favorable prognosis in gastric cancer. Mol Med Rep 2(4):589–596PubMed Enjoji M, Iida S, Sugita H, Ishikawa T, Uetake H et al (2009) BubR1 and AURKB overexpression are associated with a favorable prognosis in gastric cancer. Mol Med Rep 2(4):589–596PubMed
19.
Zurück zum Zitat Lin ZZ, Jeng YM, Hu FC, Pan HW, Tsao HW, Lai PL, Lee PH, Cheng AL, Hsu HC (2010) Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B overexpression in HCC. BMC Cancer 10:461CrossRefPubMedPubMedCentral Lin ZZ, Jeng YM, Hu FC, Pan HW, Tsao HW, Lai PL, Lee PH, Cheng AL, Hsu HC (2010) Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B overexpression in HCC. BMC Cancer 10:461CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat ZhangY JC, Li H, Lv F, Li X et al (2015) Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer. Int J Clin Exp Pathol 8(1):751–757 ZhangY JC, Li H, Lv F, Li X et al (2015) Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer. Int J Clin Exp Pathol 8(1):751–757
21.
Zurück zum Zitat Chen YJ, Chen CM, Twu NF, Yen MS, Lai CR, Wu HH, Wang PH, Yuan CC (2009) Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients. Virchows Arch 455(5):431–440CrossRefPubMed Chen YJ, Chen CM, Twu NF, Yen MS, Lai CR, Wu HH, Wang PH, Yuan CC (2009) Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients. Virchows Arch 455(5):431–440CrossRefPubMed
22.
Zurück zum Zitat Lens SM, Voest EE, Medema RH (2010) Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 10(12):825–841CrossRefPubMed Lens SM, Voest EE, Medema RH (2010) Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 10(12):825–841CrossRefPubMed
24.
Zurück zum Zitat Lok W, Klein RQ, Saif MW (2010) Aurora kinase inhibitors as anti-cancer therapy. Anti-Cancer Drugs 21(4):339–350CrossRefPubMed Lok W, Klein RQ, Saif MW (2010) Aurora kinase inhibitors as anti-cancer therapy. Anti-Cancer Drugs 21(4):339–350CrossRefPubMed
25.
Zurück zum Zitat Sehdev V, Peng D, Soutto M, Washington MK, Revetta F, Ecsedy J, Zaika A, Rau TT, Schneider-Stock R, Belkhiri A, el-Rifai W (2012) The aurora kinase A inhibitor MLN8237 enhances cisplatin-induced cell death in esophageal adenocarcinoma cells. Mol Cancer Ther 11(3):763–774CrossRefPubMedPubMedCentral Sehdev V, Peng D, Soutto M, Washington MK, Revetta F, Ecsedy J, Zaika A, Rau TT, Schneider-Stock R, Belkhiri A, el-Rifai W (2012) The aurora kinase A inhibitor MLN8237 enhances cisplatin-induced cell death in esophageal adenocarcinoma cells. Mol Cancer Ther 11(3):763–774CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Cheung CH, Sarvagalla S, Lee JY, Huang YC, Coumar MS (2014) Aurora kinase inhibitor patents and agents in clinical testing: an update (2011-2013). Expert Opin Ther Pat 24(9):1021–1038CrossRefPubMed Cheung CH, Sarvagalla S, Lee JY, Huang YC, Coumar MS (2014) Aurora kinase inhibitor patents and agents in clinical testing: an update (2011-2013). Expert Opin Ther Pat 24(9):1021–1038CrossRefPubMed
27.
Zurück zum Zitat Schwartz GK, Carvajal RD, Midgley R, Rodig SJ, Stockman PK, Ataman O, Wilson D, Das S, Shapiro GI (2013) Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. Investig New Drugs 31(2):370–380CrossRef Schwartz GK, Carvajal RD, Midgley R, Rodig SJ, Stockman PK, Ataman O, Wilson D, Das S, Shapiro GI (2013) Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. Investig New Drugs 31(2):370–380CrossRef
28.
Zurück zum Zitat Yu Y, Feng YM (2010) The role of kinesin family proteins in tumorigenesis and progression: potential biomarkers and molecular targets for cancer therapy. Cancer 116(22):5150–5160CrossRefPubMed Yu Y, Feng YM (2010) The role of kinesin family proteins in tumorigenesis and progression: potential biomarkers and molecular targets for cancer therapy. Cancer 116(22):5150–5160CrossRefPubMed
29.
Zurück zum Zitat Lee YM, Kim E, Park M, Moon E, Ahn SM, Kim W, Hwang KB, Kim YK, Choi W, Kim W (2010) Cell cycle-regulated expression and subcellular localization of a kinesin-8 member human KIF18B. Gene 466(1–2):16–25PubMed Lee YM, Kim E, Park M, Moon E, Ahn SM, Kim W, Hwang KB, Kim YK, Choi W, Kim W (2010) Cell cycle-regulated expression and subcellular localization of a kinesin-8 member human KIF18B. Gene 466(1–2):16–25PubMed
30.
Zurück zum Zitat Wu Y, Wang A, Zhu B, Huang J, Lu E (2018) KIF18B promotes tumor progression through activating the Wnt/β-catenin pathway in cervical cancer. Onco Targets Ther 11:1707–1720CrossRefPubMedPubMedCentral Wu Y, Wang A, Zhu B, Huang J, Lu E (2018) KIF18B promotes tumor progression through activating the Wnt/β-catenin pathway in cervical cancer. Onco Targets Ther 11:1707–1720CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Itzel T, Scholz P, Maass T, Krupp M, Marquardt JU, Strand S, Becker D, Staib F, Binder H, Roessler S, Wang XW, Thorgeirsson S, Müller M, Galle PR, Teufel A (2015) Translating bioinformatics in oncology: guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis. Bioinformatics 31(2):216–224CrossRefPubMed Itzel T, Scholz P, Maass T, Krupp M, Marquardt JU, Strand S, Becker D, Staib F, Binder H, Roessler S, Wang XW, Thorgeirsson S, Müller M, Galle PR, Teufel A (2015) Translating bioinformatics in oncology: guilt-by-profiling analysis and identification of KIF18B and CDCA3 as novel driver genes in carcinogenesis. Bioinformatics 31(2):216–224CrossRefPubMed
32.
Zurück zum Zitat Tanenbaum ME, Macurek L, van der Vaart B, Galli M, Akhmanova A, Medema RH (2011) A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases. Curr Biol 21(16):1356–1365CrossRefPubMed Tanenbaum ME, Macurek L, van der Vaart B, Galli M, Akhmanova A, Medema RH (2011) A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases. Curr Biol 21(16):1356–1365CrossRefPubMed
Metadaten
Titel
Bioinformatics Analysis Suggests the Combined Expression of AURKB and KIF18B Being an Important Event in the Development of Clear Cell Renal Cell Carcinoma
verfasst von
Qianqian Liu
Xiling Zhang
Haichao Tang
Jinwei Liu
Chen Fu
Mingli Sun
Lin Zhao
Minjie Wei
Zhaojin Yu
Ping Wang
Publikationsdatum
05.09.2019
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 3/2020
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00740-y

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