The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway
- Authors: Yin B.1, He M.1, Lu X.1, He C.1, Jiang D.1, Zhang H.1
-
Affiliations:
- Department of Urology, Minhang Hospital, Fudan University
- Issue: Vol 27, No 13 (2024)
- Pages: 1984-1998
- Section: Chemistry
- URL: https://kazanmedjournal.ru/1386-2073/article/view/645265
- DOI: https://doi.org/10.2174/0113862073273633231113060429
- ID: 645265
Cite item
Full Text
Abstract
Background::BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear.
Aims::This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA).
Objective::The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease.
Methods::We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays.
Results::In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels.
Conclusion::In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.
Keywords
About the authors
Bingde Yin
Department of Urology, Minhang Hospital, Fudan University
Email: info@benthamscience.net
Minke He
Department of Urology, Minhang Hospital, Fudan University
Email: info@benthamscience.net
Xuwei Lu
Department of Urology, Minhang Hospital, Fudan University
Author for correspondence.
Email: info@benthamscience.net
Chang He
Department of Urology, Minhang Hospital, Fudan University
Author for correspondence.
Email: info@benthamscience.net
Dongzhen Jiang
Department of Urology, Minhang Hospital, Fudan University
Email: info@benthamscience.net
Huawei Zhang
Department of Urology, Minhang Hospital, Fudan University
Email: info@benthamscience.net
References
- Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386. doi: 10.1002/ijc.29210 PMID: 25220842
- Qu, G.; Liu, Z.; Yang, G.; Xu, Y.; Xiang, M.; Tang, C. Development of a prognostic index and screening of prognosis related genes based on an immunogenomic landscape analysis of bladder cancer. Aging, 2021, 13(8), 12099-12112. doi: 10.18632/aging.202917 PMID: 33888644
- Lenis, A.T.; Lec, P.M.; Chamie, K.; Mshs, M. Bladder cancer. JAMA, 2020, 324(19), 1980-1991. doi: 10.1001/jama.2020.17598 PMID: 33201207
- Dy, G.W.; Gore, J.L.; Forouzanfar, M.H.; Naghavi, M.; Fitzmaurice, C. Global burden of urologic cancers, 19902013. Eur. Urol., 2017, 71(3), 437-446. doi: 10.1016/j.eururo.2016.10.008 PMID: 28029399
- Sievert, K.D.; Amend, B.; Nagele, U.; Schilling, D.; Bedke, J.; Horstmann, M.; Hennenlotter, J.; Kruck, S.; Stenzl, A. Economic aspects of bladder cancer: What are the benefits and costs? World J. Urol., 2009, 27(3), 295-300. doi: 10.1007/s00345-009-0395-z PMID: 19271220
- Humphrey, P.A.; Moch, H.; Cubilla, A.L.; Ulbright, T.M.; Reuter, V.E. The 2016 WHO classification of tumours of the urinary system and male genital organspart B: Prostate and bladder tumours. Eur. Urol., 2016, 70(1), 106-119. doi: 10.1016/j.eururo.2016.02.028 PMID: 26996659
- Saginala, K.; Barsouk, A.; Aluru, J.S.; Rawla, P.; Padala, S.A.; Barsouk, A. Epidemiology of bladder cancer. Med. Sci., 2020, 8(1), 15. doi: 10.3390/medsci8010015 PMID: 32183076
- Konety, B.; Isharwal, S. Non-muscle invasive bladder cancer risk stratification. Indian J. Urol., 2015, 31(4), 289-296.
- Lerner, S.P.; Bajorin, D.F.; Dinney, C.P.; Efstathiou, J.A.; Groshen, S.; Hahn, N.M.; Hansel, D.; Kwiatkowski, D.; ODonnell, M.; Rosenberg, J.; Svatek, R.; Abrams, J.S.; Al-Ahmadie, H.; Apolo, A.B.; Bellmunt, J.; Callahan, M.; Cha, E.K.; Drake, C.; Jarow, J.; Kamat, A.; Kim, W.; Knowles, M.; Mann, B.; Marchionni, L.; McConkey, D.; McShane, L.; Ramirez, N.; Sharabi, A.; Sharpe, A.H.; Solit, D.; Tangen, C.M.; Amiri, A.T.; Van Allen, E.; West, P.J.; Witjes, J.A.; Quale, D.Z. Summary and recommendations from the National Cancer Institutes clinical trials planning meeting on novel therapeutics for non-muscle invasive bladder cancer. Bladder Cancer, 2016, 2(2), 165-202. doi: 10.3233/BLC-160053 PMID: 27376138
- Wang, G.; Jin, W.; Xu, Z.; Ju, L.; Shan, D.; Li, S.; Yu, M.; Cao, X.; Liu, N.; Qian, K.; Zhang, Y.; Xiao, Y.; Wang, X. Urine‐based liquid biopsy in bladder cancer: Opportunities and challenges. Clin. Transl. Discov., 2023, 3(1), e176. doi: 10.1002/ctd2.176
- Bhattacharjee, S.; Sullivan, M.J.; Wynn, R.R.; Demagall, A.; Hendrix, A.S.; Sindhwani, P.; Petros, F.G.; Nadiminty, N. PARP inhibitors chemopotentiate and synergize with cisplatin to inhibit bladder cancer cell survival and tumor growth. BMC Cancer, 2022, 22(1), 312. doi: 10.1186/s12885-022-09376-9 PMID: 35321693
- Xylinas, E. Urine markers for detection and surveillance of bladder cancer. Urol. Oncol., 2014, 32(3), 222-229. doi: 10.1016/j.urolonc.2013.06.001
- Cai, Q.; Wu, Y.; Guo, Z.; Gong, R.; Tang, Y.; Yang, K.; Li, X.; Guo, X.; Niu, Y.; Zhao, Y. Urine BLCA-4 exerts potential role in detecting patients with bladder cancers: A pooled analysis of individual studies. Oncotarget, 2015, 6(35), 37500-37510. doi: 10.18632/oncotarget.6061 PMID: 26462026
- Sexton, W.J.; Wiegand, L.R.; Correa, J.J.; Politis, C.; Dickinson, S.I.; Kang, L.C. Bladder cancer: A review of non-muscle invasive disease. Cancer Contr., 2010, 17(4), 256-268. doi: 10.1177/107327481001700406 PMID: 20861813
- Narayan, V.; Vaughn, D. Pharmacokinetic and toxicity considerations in the use of neoadjuvant chemotherapy for bladder cancer. Expert Opin. Drug Metab. Toxicol., 2015, 11(5), 731-742. doi: 10.1517/17425255.2015.1005600 PMID: 25604887
- Reesink, D.J.; van de Garde, E.M.W.; Peters, B.J.M.; van der Nat, P.B.; Los, M.; Horenblas, S.; van Melick, H.H.E. Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands. Sci. Rep., 2020, 10(1), 15822. doi: 10.1038/s41598-020-72820-y PMID: 32978455
- Kaur, J.; Choi, W.; Geynisman, D.M.; Plimack, E.R.; Ghatalia, P. Role of immunotherapy in localized muscle invasive urothelial cancer. Ther. Adv. Med. Oncol., 2021, 13, 17588359211045858. PMID: 34567274
- Stenzl, A.; Cowan, N.C.; De Santis, M.; Kuczyk, M.A.; Merseburger, A.S.; Ribal, M.J.; Sherif, A.; Witjes, J.A. Treatment of muscle-invasive and metastatic bladder cancer: Update of the EAU guidelines. Eur. Urol., 2011, 59(6), 1009-1018. doi: 10.1016/j.eururo.2011.03.023 PMID: 21454009
- Yang, Z.; Xu, Y.; Bi, Y.; Zhang, N.; Wang, H.; Xing, T.; Bai, S.; Shen, Z.; Naz, F.; Zhang, Z.; Yin, L.; Shi, M.; Wang, L.; Wang, L.; Wang, S.; Xu, L.; Su, X.; Wu, S.; Yu, C. Immune escape mechanisms and immunotherapy of urothelial bladder cancer. J. Clin. Transl. Res., 2021, 7(4), 485-500. PMID: 34541363
- Wołącewicz, M.; Hrynkiewicz, R.; Grywalska, E.; Suchojad, T.; Leksowski, T.; Roliński, J.; Niedźwiedzka-Rystwej, P. Immunotherapy in bladder cancer: Current methods and future perspectives. Cancers, 2020, 12(5), 1181. doi: 10.3390/cancers12051181 PMID: 32392774
- Zucali, P.A.; Cordua, N.; DAntonio, F.; Borea, F.; Perrino, M.; De Vincenzo, F.; Santoro, A. Current perspectives on immunotherapy in the peri-operative setting of muscle-infiltrating bladder cancer. Front. Oncol., 2020, 10, 568279. doi: 10.3389/fonc.2020.568279 PMID: 33194654
- Chi, M.; Liu, J.; Mei, C.; Shi, Y.; Liu, N.; Jiang, X.; Liu, C.; Xue, N.; Hong, H.; Xie, J.; Sun, X.; Yin, B.; Meng, X.; Wang, B. TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer. J. Exp. Clin. Cancer Res., 2022, 41(1), 175. doi: 10.1186/s13046-022-02377-3 PMID: 35581606
- de Jong, J.J.; Liu, Y.; Robertson, A.G.; Seiler, R.; Groeneveld, C.S.; van der Heijden, M.S.; Wright, J.L.; Douglas, J.; DallEra, M.; Crabb, S.J.; van Rhijn, B.W.G.; van Kessel, K.E.M.; Davicioni, E.; Castro, M.A.A.; Lotan, Y.; Zwarthoff, E.C.; Black, P.C.; Boormans, J.L.; Gibb, E.A. Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis. Genome Med., 2019, 11(1), 60. doi: 10.1186/s13073-019-0669-z PMID: 31619281
- Robertson, A.G.; Kim, J.; Al-Ahmadie, H.; Bellmunt, J.; Guo, G.; Cherniack, A.D.; Hinoue, T.; Laird, P.W.; Hoadley, K.A.; Akbani, R.; Castro, M.A.A.; Gibb, E.A.; Kanchi, R.S.; Gordenin, D.A.; Shukla, S.A.; Sanchez-Vega, F.; Hansel, D.E.; Czerniak, B.A.; Reuter, V.E.; Su, X.; de Sa Carvalho, B.; Chagas, V.S.; Mungall, K.L.; Sadeghi, S.; Pedamallu, C.S.; Lu, Y.; Klimczak, L.J.; Zhang, J.; Choo, C.; Ojesina, A.I.; Bullman, S.; Leraas, K.M.; Lichtenberg, T.M.; Wu, C.J.; Schultz, N.; Getz, G.; Meyerson, M.; Mills, G.B.; McConkey, D.J.; Weinstein, J.N.; Kwiatkowski, D.J.; Lerner, S.P.; Akbani, R.; Al-Ahmadie, H.; Albert, M.; Alexopoulou, I.; Ally, A.; Antic, T.; Aron, M.; Balasundaram, M.; Bartlett, J.; Baylin, S.B.; Beaver, A.; Bellmunt, J.; Birol, I.; Boice, L.; Bootwalla, M.S.; Bowen, J.; Bowlby, R.; Brooks, D.; Broom, B.M.; Bshara, W.; Bullman, S.; Burks, E.; Cárcano, F.M.; Carlsen, R.; Carvalho, B.S.; Carvalho, A.L.; Castle, E.P.; Castro, M.A.A.; Castro, P.; Catto, J.W.; Chagas, V.S.; Cherniack, A.D.; Chesla, D.W.; Choo, C.; Chuah, E.; Chudamani, S.; Cortessis, V.K.; Cottingham, S.L.; Crain, D.; Curley, E.; Czerniak, B.A.; Daneshmand, S.; Demchok, J.A.; Dhalla, N.; Djaladat, H.; Eckman, J.; Egea, S.C.; Engel, J.; Felau, I.; Ferguson, M.L.; Gardner, J.; Gastier-Foster, J.M.; Gerken, M.; Getz, G.; Gibb, E.A.; Gomez-Fernandez, C.R.; Gordenin, D.A.; Guo, G.; Hansel, D.E.; Harr, J.; Hartmann, A.; Herbert, L.M.; Hinoue, T.; Ho, T.H.; Hoadley, K.A.; Holt, R.A.; Hutter, C.M.; Jones, S.J.M.; Jorda, M.; Kahnoski, R.J.; Kanchi, R.S.; Kasaian, K.; Kim, J.; Klimczak, L.J.; Kwiatkowski, D.J.; Lai, P.H.; Laird, P.W.; Lane, B.R.; Leraas, K.M.; Lerner, S.P.; Lichtenberg, T.M.; Liu, J.; Lolla, L.; Lotan, Y.; Lu, Y.; Lucchesi, F.R.; Ma, Y.; Machado, R.D.; Maglinte, D.T.; Mallery, D.; Marra, M.A.; Martin, S.E.; Mayo, M.; McConkey, D.J.; Meraney, A.; Meyerson, M.; Mills, G.B.; Moinzadeh, A.; Moore, R.A.; Mora Pinero, E.M.; Morris, S.; Morrison, C.; Mungall, K.L.; Mungall, A.J.; Myers, J.B.; Naresh, R.; ODonnell, P.H.; Ojesina, A.I.; Parekh, D.J.; Parfitt, J.; Paulauskis, J.D.; Sekhar Pedamallu, C.; Penny, R.J.; Pihl, T.; Porten, S.; Quintero-Aguilo, M.E.; Ramirez, N.C.; Rathmell, W.K.; Reuter, V.E.; Rieger-Christ, K.; Robertson, A.G.; Sadeghi, S.; Saller, C.; Salner, A.; Sanchez-Vega, F.; Sandusky, G.; Scapulatempo-Neto, C.; Schein, J.E.; Schuckman, A.K.; Schultz, N.; Shelton, C.; Shelton, T.; Shukla, S.A.; Simko, J.; Singh, P.; Sipahimalani, P.; Smith, N.D.; Sofia, H.J.; Sorcini, A.; Stanton, M.L.; Steinberg, G.D.; Stoehr, R.; Su, X.; Sullivan, T.; Sun, Q.; Tam, A.; Tarnuzzer, R.; Tarvin, K.; Taubert, H.; Thiessen, N.; Thorne, L.; Tse, K.; Tucker, K.; Van Den Berg, D.J.; van Kessel, K.E.; Wach, S.; Wan, Y.; Wang, Z.; Weinstein, J.N.; Weisenberger, D.J.; Wise, L.; Wong, T.; Wu, Y.; Wu, C.J.; Yang, L.; Zach, L.A.; Zenklusen, J.C.; Zhang, J.J.; Zhang, J.; Zmuda, E.; Zwarthoff, E.C. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell, 2017, 171(3), 540-556.e25. doi: 10.1016/j.cell.2017.09.007 PMID: 28988769
- Wullweber, A.; Strick, R.; Lange, F.; Sikic, D.; Taubert, H.; Wach, S.; Wullich, B.; Bertz, S.; Weyerer, V.; Stoehr, R.; Breyer, J.; Burger, M.; Hartmann, A.; Strissel, P.L.; Eckstein, M. Bladder tumor subtype commitment occurs in carcinoma in situ driven by key signaling pathways including ECM remodeling. Cancer Res., 2021, 81(6), 1552-1566. doi: 10.1158/0008-5472.CAN-20-2336 PMID: 33472889
- Tran, L.; Xiao, J.F.; Agarwal, N.; Duex, J.E.; Theodorescu, D. Advances in bladder cancer biology and therapy. Nat. Rev. Cancer, 2021, 21(2), 104-121. doi: 10.1038/s41568-020-00313-1 PMID: 33268841
- Alfred Witjes, J.; Lebret, T.; Compérat, E.M.; Cowan, N.C.; De Santis, M.; Bruins, H.M.; Hernández, V.; Espinós, E.L.; Dunn, J.; Rouanne, M.; Neuzillet, Y.; Veskimäe, E.; van der Heijden, A.G.; Gakis, G.; Ribal, M.J. Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur. Urol., 2017, 71(3), 462-475. doi: 10.1016/j.eururo.2016.06.020 PMID: 27375033
- Kim, E-J. Clinical implications and prognostic values of topoisomerase-II alpha expression in primary non-muscle-invasive bladder cancer. Urology, 2010, 75(6), 1516.e9-13. doi: 10.1016/j.urology.2009.08.055
- Liu, J.; Zhou, S.; Li, S.; Jiang, Y.; Wan, Y.; Ma, X.; Cheng, W. Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis. Cancer Cell Int., 2019, 19(1), 136. doi: 10.1186/s12935-019-0859-1 PMID: 31139013
- Basso, K.; Margolin, A.A.; Stolovitzky, G.; Klein, U.; Dalla-Favera, R.; Califano, A. Reverse engineering of regulatory networks in human B cells. Nat. Genet., 2005, 37(4), 382-390. doi: 10.1038/ng1532 PMID: 15778709
- Zeng, S.; Yu, X.; Ma, C.; Song, R.; Zhang, Z.; Zi, X.; Chen, X.; Wang, Y.; Yu, Y.; Zhao, J.; Wei, R.; Sun, Y.; Xu, C. Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma. Sci. Rep., 2017, 7(1), 3151. doi: 10.1038/s41598-017-02990-9 PMID: 28600503
- Mitra, A.P. Molecular substratification of bladder cancer: Moving towards individualized patient management. Ther. Adv. Urol., 2016, 8(3), 215-233. doi: 10.1177/1756287216638981 PMID: 27247631
- Liu, X.; Hu, A.X.; Zhao, J.L.; Chen, F.L. Identification of key gene modules in human osteosarcoma by co‐expression analysis weighted gene co‐expression network analysis (WGCNA). J. Cell. Biochem., 2017, 118(11), 3953-3959. doi: 10.1002/jcb.26050 PMID: 28398605
- Shuai, M.; He, D.; Chen, X. Optimizing weighted gene co-expression network analysis with a multi-threaded calculation of the topological overlap matrix. Stat. Appl. Genet. Mol. Biol., 2021, 20(4-6), 145-153. doi: 10.1515/sagmb-2021-0025 PMID: 34757703
- Ko, D.K.; Brandizzi, F. Coexpression network construction and visualization from transcriptomes underlying ER stress responses. In: Plant Proteostasis: Methods and Protocols; Springer, 2022; pp. 385-401.
- Wang, Y.; Liu, T.; Liu, Y.; Chen, J.; Xin, B.; Wu, M.; Cui, W. Coronary artery disease associated specific modules and feature genes revealed by integrative methods of WGCNA, MetaDE and machine learning. Gene, 2019, 710, 122-130. doi: 10.1016/j.gene.2019.05.010 PMID: 31075415
- Wu, J.; Liu, X.J.; Hu, J.N.; Liao, X.H.; Lin, F.F. Transcriptomics and prognosis analysis to identify critical biomarkers in invasive breast carcinoma. Technol. Cancer Res. Treat., 2020, 19, 1533033820957011. doi: 10.1177/1533033820957011 PMID: 33176622
- Park, Y.; Heider, D.; Hauschild, A.C. Integrative analysis of next-generation sequencing for next-generation cancer research toward artificial intelligence. Cancers, 2021, 13(13), 3148. doi: 10.3390/cancers13133148 PMID: 34202427
- Zhou, Z.; Liu, S.; Zhang, M.; Zhou, R.; Liu, J.; Chang, Y.; Zhao, Q. Overexpression of topoisomerase 2-alpha confers a poor prognosis in pancreatic adenocarcinoma identified by co-expression analysis. Dig. Dis. Sci., 2017, 62(10), 2790-2800. doi: 10.1007/s10620-017-4718-4 PMID: 28815403
- Blum, A.; Wang, P.; Zenklusen, J.C. SnapShot: TCGA-analyzed tumors. Cell, 2018, 173(2), 530. doi: 10.1016/j.cell.2018.03.059 PMID: 29625059
- Loeb, L.A.; Monnat, R.J., Jr DNA polymerases and human disease. Nat. Rev. Genet., 2008, 9(8), 594-604. doi: 10.1038/nrg2345 PMID: 18626473
- Briggs, S.; Tomlinson, I. Germline and somatic polymerase ϵ and δ mutations define a new class of hypermutated colorectal and endometrial cancers. J. Pathol., 2013, 230(2), 148-153. doi: 10.1002/path.4185 PMID: 23447401
- Zhang, P.; Chen, X.; Zhang, L.; Cao, D.; Chen, Y.; Guo, Z.; Chen, J. POLE2 facilitates the malignant phenotypes of glioblastoma through promoting AURKA-mediated stabilization of FOXM1. Cell Death Dis., 2022, 13(1), 61. doi: 10.1038/s41419-021-04498-7 PMID: 35039475
- Zhu, Y.; Chen, G.; Song, Y.; Chen, Z.; Chen, X. POLE2 knockdown reduce tumorigenesis in esophageal squamous cells. Cancer Cell Int., 2020, 20(1), 388. doi: 10.1186/s12935-020-01477-4 PMID: 32831648
- Liu, D.; Zhang, X.X.; Xi, B.X.; Wan, D.Y.; Li, L.; Zhou, J.; Wang, W.; Ma, D.; Wang, H.; Gao, Q.L. Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer. Int. J. Oncol., 2014, 45(3), 1232-1240. doi: 10.3892/ijo.2014.2510 PMID: 24970368
- Li, J.; Wang, J.; Yu, J.; Zhao, Y.; Dong, Y.; Fan, Y.; Li, N.; Zhang, Y.; Wang, Y. Knockdown of POLE2 expression suppresses lung adenocarcinoma cell malignant phenotypes in vitro. Oncol. Rep., 2018, 40(5), 2477-2486. doi: 10.3892/or.2018.6659 PMID: 30132567
- Pearlman, A.; Rahman, M.T.; Upadhyay, K.; Loke, J.; Ostrer, H. Ectopic Otoconin 90 expression in triple negative breast cancer cell lines is associated with metastasis functions. PLoS One, 2019, 14(2), e0211737. doi: 10.1371/journal.pone.0211737 PMID: 30763339
- Lv, Z.; Wu, X.; Lu, P.; Xu, X.; Wang, J.; Zhang, C.; Liu, W.; Gao, Y.; Lu, C.; Zhang, Y.; Kou, H. POLE2 knockdown suppresses lymphoma progression via downregulating Wnt/β-catenin signaling pathway. Mol. Cell. Biochem., 2023, 479, 487-497. doi: 10.1007/s11010-023-04738-8 PMID: 37097331
- Aoki, M.; Fujishita, T. Oncogenic roles of the PI3K/AKT/mTOR axis. Curr. Top. Microbiol. Immunol., 2017, 407, 153-189. doi: 10.1007/82_2017_6 PMID: 28550454
- Su, Y.L.; Luo, H.L.; Huang, C.C.; Liu, T.T.; Huang, E.Y.; Sung, M.T.; Lin, J.J.; Chiang, P.H.; Chen, Y.T.; Kang, C.H.; Cheng, Y.T. Galectin-1 overexpression activates the FAK/PI3K/AKT/mTOR pathway and is correlated with upper urinary urothelial carcinoma progression and survival. Cells, 2020, 9(4), 806. doi: 10.3390/cells9040806 PMID: 32225123
- Yao, J.; Qian, K.; Chen, C.; Liu, X.; Yu, D.; Yan, X.; Liu, T.; Li, S. ZNF139/circZNF139 promotes cell proliferation, migration and invasion via activation of PI3K/AKT pathway in bladder cancer. Aging, 2020, 12(10), 9915-9934. doi: 10.18632/aging.103256 PMID: 32454461
- Pelucchi, C.; Bosetti, C.; Negri, E.; Malvezzi, M.; La Vecchia, C. Mechanisms of Disease: The epidemiology of bladder cancer. Nat. Clin. Pract. Urol., 2006, 3(6), 327-340. doi: 10.1038/ncpuro0510 PMID: 16763645
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249. doi: 10.3322/caac.21660 PMID: 33538338
- Hatta, M.N.A.; Mohamad Hanif, E.A.; Chin, S.F.; Neoh, H. Pathogens and carcinogenesis: A review. Biology, 2021, 10(6), 533. doi: 10.3390/biology10060533 PMID: 34203649
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin., 2022, 72(1), 7-33. doi: 10.3322/caac.21708 PMID: 35020204
- Xia, C.; Dong, X.; Li, H.; Cao, M.; Sun, D.; He, S.; Yang, F.; Yan, X.; Zhang, S.; Li, N.; Chen, W. Cancer statistics in China and United States, 2022: Profiles, trends, and determinants. Chin. Med. J., 2022, 135(5), 584-590. doi: 10.1097/CM9.0000000000002108 PMID: 35143424
- von der Maase, H.; Hansen, S.W.; Roberts, J.T.; Dogliotti, L.; Oliver, T.; Moore, M.J.; Bodrogi, I.; Albers, P.; Knuth, A.; Lippert, C.M.; Kerbrat, P.; Sanchez Rovira, P.; Wersall, P.; Cleall, S.P.; Roychowdhury, D.F.; Tomlin, I.; Visseren-Grul, C.M.; Conte, P.F. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large, randomized, multinational, multicenter, phase III study. J. Clin. Oncol., 2000, 18(17), 3068-3077. doi: 10.1200/JCO.2000.18.17.3068 PMID: 11001674
- Aggen, D.H.; Drake, C.G. Biomarkers for immunotherapy in bladder cancer: A moving target. J. Immunother. Cancer, 2017, 5(1), 94. doi: 10.1186/s40425-017-0299-1 PMID: 29157296
- Flaig, T.W.; Spiess, P.E.; Agarwal, N.; Bangs, R.; Boorjian, S.A.; Buyyounouski, M.K.; Chang, S.; Downs, T.M.; Efstathiou, J.A.; Friedlander, T.; Greenberg, R.E.; Guru, K.A.; Guzzo, T.; Herr, H.W.; Hoffman-Censits, J.; Hoimes, C.; Inman, B.A.; Jimbo, M.; Kader, A.K.; Lele, S.M.; Michalski, J.; Montgomery, J.S.; Nandagopal, L.; Pagliaro, L.C.; Pal, S.K.; Patterson, A.; Plimack, E.R.; Pohar, K.S.; Preston, M.A.; Sexton, W.J.; Siefker-Radtke, A.O.; Tward, J.; Wright, J.L.; Gurski, L.A.; Johnson-Chilla, A. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2020, 18(3), 329-354. doi: 10.6004/jnccn.2020.0011 PMID: 32135513
- Gilyazova, I.; Enikeeva, K.; Rafikova, G.; Kagirova, E.; Sharifyanova, Y.; Asadullina, D.; Pavlov, V. Epigenetic and immunological features of bladder cancer. Int. J. Mol. Sci., 2023, 24(12), 9854. doi: 10.3390/ijms24129854 PMID: 37373000
- Markman, M.; Mekhail, T.M. Paclitaxel in cancer therapy. Expert Opin. Pharmacother., 2002, 3(6), 755-766. doi: 10.1517/14656566.3.6.755 PMID: 12036415
- Yi, L.; Wang, H.; Li, W.; Ye, K.; Xiong, W.; Yu, H.; Jin, X. The FOXM1/RNF26/p57 axis regulates the cell cycle to promote the aggressiveness of bladder cancer. Cell Death Dis., 2021, 12(10), 944. doi: 10.1038/s41419-021-04260-z PMID: 34650035
- Roh, Y.G.; Mun, J.Y.; Kim, S.K.; Park, W.Y.; Jeong, M.S.; Kim, T.N.; Kim, W.T.; Choi, Y.H.; Chu, I.S.; Leem, S.H. Fanconi anemia pathway activation by FOXM1 is critical to bladder cancer recurrence and anticancer drug resistance. Cancers, 2020, 12(6), 1417. doi: 10.3390/cancers12061417 PMID: 32486251
- Yap, D.B.S.; Hsieh, J.K.; Chan, F.S.G.; Lu, X. mdm2: A bridge over the two tumour suppressors, p53 and Rb. Oncogene, 1999, 18(53), 7681-7689. doi: 10.1038/sj.onc.1202954 PMID: 10618708
- Geva‐Zatorsky, N. Oscillations and variability in the p53 system. Mol. Syst. Biol., 2006, 2, 2006.0033. doi: 10.1038/msb4100068
- Shi, T.; Yuan, Z.; He, Y.; Zhang, D.; Chen, S.; Wang, X.; Yao, L.; Shao, J.; Wang, X. Competition between p53 and YY1 determines PHGDH expression and malignancy in bladder cancer. Cell. Oncol., 2023. doi: 10.1007/s13402-023-00823-8 PMID: 37326803
- Yang, Z. Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signalling pathway in bladder cancer. FEBS Open Bio, 2021, 11(9), 2631-2646.
- Long, X. Network-based pharmacology and in vitro validation reveal that galangin induces apoptosis in bladder cancer cells by promoting the p53 signaling pathway. Anticancer. Agents Med. Chem., 2023, 23(7), 847-857. PMID: 36305128
- Ye, G.; Kan, S.; Chen, J.; Lu, X. Puerarin in inducing apoptosis of bladder cancer cells through inhibiting SIRT1/p53 pathway. Oncol. Lett., 2019, 17(1), 195-200. PMID: 30655755
- Chen, S. ANLN serves as an oncogene in bladder urothelial carcinoma via activating JNK signaling pathway. Urol. Int., 2023, 107(3), 310-320. PMID: 35504258
- Wu, S.; Nitschke, K.; Heinkele, J.; Weis, C.A.; Worst, T.S.; Eckstein, M.; Porubsky, S.; Erben, P. ANLN and TLE2 in muscle invasive bladder cancer: A functional and clinical evaluation based on in silico and in vitro data. Cancers, 2019, 11(12), 1840. doi: 10.3390/cancers11121840 PMID: 31766561
- Wu, Z.; Wang, Y.M.; Dai, Y.; Chen, L.A. POLE2 serves as a prognostic biomarker and is associated with immune infiltration in squamous cell lung cancer. Med. Sci. Monit., 2020, 26, e921430-e921431. doi: 10.12659/MSM.921430 PMID: 32304567
- Ma, X.; Dong, L.; Liu, X.; Ou, K.; Yang, L. POLE/POLD1 mutation and tumor immunotherapy. J. Exp. Clin. Cancer Res., 2022, 41(1), 216. doi: 10.1186/s13046-022-02422-1 PMID: 35780178
- Kachrilas, S.; Dellis, A.; Papatsoris, A.; Avgeris, S.; Anastasiou, D.; Gavriil, A.; Horti, M.; Tseleni Balafouta, S.; Livadas, K.; Stravopodis, D.J.; Alivizatos, G.; Voutsinas, G.E.; Deliveliotis, C. PI3K/AKT pathway genetic alterations and dysregulation of expression in bladder cancer. J. BUON, 2019, 24(1), 329-337. PMID: 30941989
- Qian, Y.; Deng, J.; Xie, H.; Geng, L.; Zhou, L.; Wang, Y.; Yin, S.; Feng, X.; Zheng, S. Regulation of TLR4-induced IL-6 response in bladder cancer cells by opposing actions of MAPK and PI3K signaling. J. Cancer Res. Clin. Oncol., 2009, 135(3), 379-386. doi: 10.1007/s00432-008-0478-z PMID: 18825409
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