Prognostic value analysis of TOP2A gene expression for bladder cancer

doi:10.3760/cma.j.issn.1673-422X.2018.01.005

Abstract

Abstract: ObjectiveTo investigate the relationship between DNA topoisomerase Ⅱα (TOP2A) gene expression and clinicopathological characteristics and its significance of prognostic evaluation for patients with bladder cancer. MethodsBladder cancer gene expression profile GSE13507 (n=165) and GSE31189 (n=52) were obtained. The expression profile and clinical information of patients with bladder cancer were retrospectively analyzed, and the survival analysis was made. Gene set enrichment analysis (GSEA) was conducted to explore the related pathways which were regulated by TOP2A. ResultsCompared with normal bladder tissues, TOP2A was upregulated in bladder cancer tissues (5.823±1.079 vs. 4.820±1.129), with a statistically significant difference (t=4.336, P＜0.001). The TOP2A gene expression in patients with bladder cancer was correlated with the age of patients (χ2=5.926, P=0.015), sex (χ2=6.046, P=0.014), T staging (χ2=19.484, P＜0.001), N staging (χ2=9.178, P=0.002), M staging (χ2=21.142, P＜0.001), tumor grade (χ2=47.005, P＜0.001), and progression (χ2=11.735, P=0.001), but it was not correlated with recurrence (χ2=0.808, P=0.369). Survival analysis showed that the specific survival rate in the 100 months of TOP2A gene high expression group and low expression group had a statistically significant difference (66.59% vs. 87.95%, χ2=15.820, P＜0.001). The median overall survival time of TOP2A gene high expression group and low expression group were 51.77 months and 134.97 months respectively, with a statistically significant difference (χ2=11.280, P=0.008). The results of GSEA indicated that TOP2A could regulate gene sets related with several pathways like MYCV1 signaling (P=0.035, FDR=0.132), MYCV2 signaling (P=0.012, FDR=0.058), E2F signaling (P<0.001, FDR=0.006) and G2M checkpoint (P=0.006, FDR=0.044). ConclusionThe TOP2A gene expression is closely related with clinicopathological characteristics of patients with bladder cancer. TOP2A may function as a potential marker of prognosis for patients with bladder cancer.

Key words: DNA topoisomerases, type Ⅱ, Urinary bladder neoplasms, Gene expression, Prognosis

Yuan Jiayi, He Hengjing, Bi Yaqiong, Guo Zixin, Xiao Yu, Li Sheng. Prognostic value analysis of TOP2A gene expression for bladder cancer[J]. Journal of International Oncology, 2018, 45(1): 22-.

References

［1］ Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis［J］. Urology, 2005, 66 (6 Suppl 1): 434. DOI: 10.1016/j.urology.2005.07.062. ［2］ Li S, Zeng XT, Ruan XL, et al. Association between XPD Lys751Gln polymorphism and bladder cancer susceptibility: an updated and cumulative metaanalysis based on 6,836 cases and 8,251 controls［J］. Mol Biol Rep, 2014, 41(6): 36213629. DOI: 10.1007/s1103301432262. ［3］ Wijkstrm H, Norming U, Lagerkvist M, et al. Evaluation of clinical staging before cystectomy in transitional cell bladder carcinoma: a longterm followup of 276 consecutive patients［J］. Br J Urol, 1998, 81(5): 686691. ［4］ Demel HR, Feuerecker B, Piontek G, et al. Effects of topoisomerase inhibitors that induce DNA damage response on glucose metabolism and PI3K/Akt/mTOR signaling in multiple myeloma cells［J］. Am J Cancer Res, 2015, 5(5): 16491664. ［5］ Cao B, Chen H, Gao Y, et al. CIP36, a novel topoisomerase Ⅱtargeting agent, induces the apoptosis of multidrugresistant cancer cells in vitro［J］. Int J Mol Med, 2015, 35(3): 771776. DOI: 10.3892/ijmm.2015.2068. ［6］ Akagi T, Ito T, Kato M, et al. Chromosomal abnormalities and novel diseaserelated regions in progression from Barrett′s esophagus to esophageal adenocarcinoma［J］. Int J Cancer, 2009, 125(10): 23492359. DOI: 10.1002/ijc.24620. ［7］ Kim WJ, Kim EJ, Kim SK, et al. Predictive value of progressionrelated gene classifier in primary nonmuscle invasive bladder cancer［J］. Mol Cancer, 2010, 9: 3. DOI: 10.1186/1476459893. ［8］ Lee JS, Leem SH, Lee SY, et al. Expression signature of E2F1 and its associated genes predict superficial to invasive progression of bladder tumors［J］. J Clin Oncol, 2010, 28(16): 26602667. DOI: 10.1200/JCO.2009.25.0977. ［9］ Urquidi V, Goodison S, Cai Y, et al. A candidate molecular biomarker panel for the detection of bladder cancer［J］. Cancer Epidemiol Biomarkers Prev, 2012, 21(12): 21492158. DOI: 10.1158/10559965.EPI120428. ［10］ Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledgebased approach for interpreting genomewide expression profiles［J］. Proc Natl Acad Sci USA, 2005, 102(43): 1554515550. DOI: 10.1073/pnas.0506580102. ［11］ Mootha VK, Lindgren CM, Eriksson KF, et al. PGC1alpharesponsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes［J］. Nat Genet, 2003, 34(3): 267273. DOI: 10.1038/ng1180. ［12］ Jain CK, Roychoudhury S, Majumder HK. Selective killing of G2 decatenation checkpoint defective colon cancer cells by catalytic topoisomerase Ⅱ inhibitor［J］. Biochim Biophys Acta, 2015, 1853 (5): 11951204. DOI: 10.1016/j.bbamcr.2015.02.021. ［13］ Lin HF, Huang HL, Liao JF, et al. Dicentrine analogueinduced G2/M arrest and apoptosis through inhibition of topoisomerase Ⅱ activity in human cancer cells［J］. Planta Med, 2015, 81(10): 830837. DOI: 10.1055/s00351546128. ［14］汤小江, 周瑜辉, 张伟, 等. TOP2A基因表达与乳腺癌HER2通路的相关性［J］. 西安交通大学学报(医学版), 2015, 36(4): 519522, 557. DOI: 10.7652/jdyxb201504019. ［15］韩正祥, 张梦瑾, 张英楠, 等. TOP2A在非小细胞肺癌中的高表达促进肿瘤细胞的增殖和侵袭能力［J］. 现代肿瘤医学, 2016, 24(9): 13711375. DOI: 10.3969/j.issn.16724992.2016.09.011. ［16］ Morgan TM, Clark PE. Bladder cancer［J］. Curr Opin Oncol, 2010, 22(3): 242249. DOI: 10.1097/CCO.0b013e3283378c6b. ［17］郭巍, 陈美霓, 王爱红, 等. P53、Bcl2和Bax在膀胱癌的表达及意义［J］. 山西医科大学学报, 2014, 45(3): 180182. DOI: 10.3969/J.ISSN.10076611.2014.03.006. ［18］邢发枢, 陈湘, 陈早庆, 等. 膀胱癌Ki67的表达在临床应用的研究［J］. 中国现代医学杂志, 2009, 19(19): 30083010. ［19］ Simon R, Atefy R, Wagner U, et al. HER2 and TOP2A coamplification in urinary bladder cancer［J］. Int J Cancer, 2003, 107(5): 764772. DOI: 10.1002/ijc.11477. ［20］ Raspollini MR, Luque RJ, Menendez CL, et al. T1 highgrade bladder carcinoma outcome: the role of p16, topoisomeraseⅡα, survivin, and Ecadherin［J］. Hum Pathol, 2016, 57: 7884. DOI: 10.1016/j.humpath.2016.06.022. ［21］ Liu HQ, Zhang SL, Song S. HER2/neu and TOPⅡa expression in gastric cancer reflect disease severity［J］. Hepatogastroenterology, 2012, 59(116): 12901293. DOI: 10.5754/hge11844. ［22］冯春琼, 邹亚光, 周其赵, 等. GSEA在全基因组表达谱芯片数据分析中的应用［J］. 现代生物医学进展, 2009, 9(13): 25532557. DOI: 10.13241/j.cnki.pmb.2009.13.004.

[1]	Qian Xiaotao, Shi Ziyi, Hu Ge, Wu Xiaowei. Efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma： a real-world clinical study [J]. Journal of International Oncology, 2024, 51(6): 326-331.
[2]	Yang Mi, Bie Jun, Zhang Jiayong, Deng Jiaxiu, Tang Zuge, Lu Jun. Analysis of the efficacy and prognosis of neoadjuvant therapy for locally advanced resectable esophageal cancer [J]. Journal of International Oncology, 2024, 51(6): 332-337.
[3]	Fan Zhipeng, Yu Jing, Hu Jing, Liao Zhengkai, Xu Yu, Ouyang Wen, Xie Conghua. Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy [J]. Journal of International Oncology, 2024, 51(5): 257-266.
[4]	Yang Lin, Lu Ning, Wen Hua, Zhang Mingxin, Zhu Lin. Study on the clinical relationship between inflammatory burden index and gastric cancer [J]. Journal of International Oncology, 2024, 51(5): 274-279.
[5]	Liu Pingping, He Xuefang, Zhang Yi, Yang Xu, Zhang Shanshan, Ji Yifei. Risk factors of postoperative recurrence in patients with primary brain glioma and prediction model construction [J]. Journal of International Oncology, 2024, 51(4): 193-197.
[6]	Wan Fang, Yang Gang, Li Rui, Wan Qijing. Expression levels and clinical significance of serum miR-497 and miR-383 in patients with esophageal cancer [J]. Journal of International Oncology, 2024, 51(4): 204-209.
[7]	Yao Yixin, Shen Yulin. Predictive value of serum SOCS3 and TXNIP levels for the prognosis of patients with hepatocellular carcinoma treated with TACE [J]. Journal of International Oncology, 2024, 51(4): 217-222.
[8]	Sun Weiwei, Yao Xuemin, Wang Pengjian, Wang Jing, Jia Jinghao. Exploration of prognostic factors and nomogram construction for advanced non-small cell lung cancer treated with immunotherapy based on hematologic indexes [J]. Journal of International Oncology, 2024, 51(3): 143-150.
[9]	Liu Yulan, Jing Haiyan, Sun Jing, Song Wei, Sha Dan. Advances in predicting efficacy and prognostic markers of immunotherapy for gastric cancer [J]. Journal of International Oncology, 2024, 51(3): 175-180.
[10]	Peng Qin, Cai Yuting, Wang Wei. Advances on KPNA2 in liver cancer [J]. Journal of International Oncology, 2024, 51(3): 181-185.
[11]	Chen Boguang, Wang Sugui, Zhang Yongjie. Role of serum cholinesterase and inflammatory markers in the prognosis of stage ⅠA -ⅢA breast cancer [J]. Journal of International Oncology, 2024, 51(2): 73-82.
[12]	Jin Xudong, Chen Zhongjian, Mao Weimin. Research progress on the role of MTAP in malignant mesothelioma [J]. Journal of International Oncology, 2024, 51(2): 99-104.
[13]	Huang Zhen, Chen Yongshun. Research progress of circulating tumor DNA in the diagnosis and treatment of hepatocellular carcinoma [J]. Journal of International Oncology, 2024, 51(1): 59-64.
[14]	Wang Xiao, Li Ying, Luo Yujie, Jin Shu. Study on the prognostic value of serological indicators for nasopharyngeal carcinoma based on nomogram model [J]. Journal of International Oncology, 2023, 50(8): 463-469.
[15]	Liu Debao, Sun Ziwen, Lu Shoutang, Xu Haidong. Expression and clinical significance of ASB6 in colorectal cancer tissues [J]. Journal of International Oncology, 2023, 50(8): 470-474.