Expression, association with clinicopathological features and prognostic potential of CEP55, p‑Akt, FoxM1 and MMP‑2 in astrocytoma

Nie,Saisai; Lou,Lei; Wang,Juan; Cui,Jinfeng; Wu,Wenxin; Zhang,Qing; Liu,Ying; Su,Lingrui; Chang,Ying; Guo,Wenli; Shen,Haitao; Xing,Lingxiao; Li,Yuehong

doi:10.3892/ol.2020.11742

Expression, association with clinicopathological features and prognostic potential of CEP55, p‑Akt, FoxM1 and MMP‑2 in astrocytoma

Authors:
- Saisai Nie
- Lei Lou
- Juan Wang
- Jinfeng Cui
- Wenxin Wu
- Qing Zhang
- Ying Liu
- Lingrui Su
- Ying Chang
- Wenli Guo
- Haitao Shen
- Lingxiao Xing
- Yuehong Li
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Affiliations: Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Laboratory of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Published online on: June 17, 2020 https://doi.org/10.3892/ol.2020.11742
Pages: 1685-1694
Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Centrosomal protein 55 (CEP55) is a member of the centrosomal‑associated protein family and participates in the regulation of cytokinesis during cell mitosis. However, aberrant CEP55 protein expression has been observed in human tumors. In addition, CEP55 regulates the biological functions of tumors by inducing the Akt pathway and upregulating forkhead box protein M1 (FoxM1) and matrix metalloproteinase‑2 (MMP‑2). In the present study, the levels, clinicopathological features and prognostic potential of CEP55, phosphorylated Akt (p‑Akt), FoxM1 and MMP‑2 in astrocytoma were evaluated. CEP55, p‑Akt, FoxM1 and MMP‑2 levels were examined in 27 normal brain tissues and 262 astrocytoma tissues by using immunohistochemistry. Furthermore, Kaplan‑Meier analysis and Cox proportional hazards models were applied to predict the prognosis of patients with astrocytoma. The results indicated that expression levels of CEP55 and other proteins were elevated in human astrocytoma compared with those in normal brain tissue. The levels of the selected proteins were increased as the tumor grade increased. Furthermore, CEP55 expression was positively correlated with p‑Akt, FoxM1 and MMP‑2 levels in astrocytoma. Overall survival analysis revealed that patient prognosis was associated with CEP55, p‑Akt, FoxM1 and MMP‑2 levels, as well as with the tumor grade and patient age. Furthermore, CEP55, FoxM1, tumor grade and patient age were independent prognostic factors in astrocytoma according to multivariate analysis. Taken together, the present results suggested that CEP55, p‑Akt, FoxM1 and MMP‑2 have crucial roles in the progression and prognosis of human astrocytoma and that CEP55 and FoxM1 may be potential therapeutic targets.

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1	Surawicz TS, Davis F, Freels S, Laws ER Jr and Menck HR: Brain tumor survival: Results from the national cancer data base. J Neurooncol. 40:151–160. 1998. View Article : Google Scholar : PubMed/NCBI
2	Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsk Y, Kruchko C and Barnholtz-Sloan JS: CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro Oncol. 17 (Suppl 4):iv1S–iv62S. 2015. View Article : Google Scholar
3	Agnihotri S, Alddape KD and Zadeh G: Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma. Neurosurg Focus. 37:E132014. View Article : Google Scholar : PubMed/NCBI
4	Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, et al: IDH1 and IDH2 mutations in gliomas. N Engl J Med. 360:765–73. 2009. View Article : Google Scholar : PubMed/NCBI
5	Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P and Ellison DW: The 2016 world health organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 131:803–820. 2016. View Article : Google Scholar : PubMed/NCBI
6	Fabbro M, Zhou BB, Takahashi M, Sarcevic B, Lal P, Graham ME, Gabrielli BG, Robinson PJ, Niqq EA, Ono Y and Khanna KK: Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Dev cell. 9:477–488. 2005. View Article : Google Scholar : PubMed/NCBI
7	Singh PK, Srivastava AK, Rath SK, Dalela D, Goel MM and Bhatt ML: Expression and clinical significance of centrosomal protein 55 (CEP55) in human urinary bladder transitiona-l cell carcinoma. Immunobiology. 220:103–108. 2015. View Article : Google Scholar : PubMed/NCBI
8	Jiang W, Wang Z and Jia Y: CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma. Oncol Lett. 13:236–242. 2017. View Article : Google Scholar : PubMed/NCBI
9	Qi J, Liu G and Wang F: High levels of centrosomal protein 55 expression is associated with poor clinical prognosis in patients with cervical cancer. Oncol Lett. 15:9347–9352. 2018.PubMed/NCBI
10	Tao J, Zhi X, Tian Y, Li Z, Zhu Y, Wang W, Xie K, Tang J, Zhang X, Wang L and Xu Z: CEP55 contributes to human gastric carcinoma by regulating cell proliferation. Tumour Biol. 35:4389–4399. 2014. View Article : Google Scholar : PubMed/NCBI
11	Chen CH, Lu PJ, Chen YC, Fu SL, Wu KJ, Tsou AP, Lee YCG, Lin TCE, Hsu SL, Lin WJ, et al: FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway. Oncogene. 26:4272–4283. 2007. View Article : Google Scholar : PubMed/NCBI
12	Jeffery J, Sinha D, Srihari S, Kalimutho M and Khanna KK: Beyond cytokinesis: The emerging roles of CEP55 in tumorigenesis. Oncogene. 35:683–690. 2016. View Article : Google Scholar : PubMed/NCBI
13	Xu L, Xia C, Sheng F, Sun Q, Xiong J and Wang S: CEP55 promotes the proliferation and invasion of tumour cells via the AKT signalling pathway in osteosarcoma. Carcinogenesis. 39:623–631. 2018. View Article : Google Scholar : PubMed/NCBI
14	Chen CH, Lai JM, Chou TY, Chen CY, Su LJ, Lee YC, Cheng TS, Hong YR, Chou CK, Whang-Peng J, et al: VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway. PLoS One. 4:e50522009. View Article : Google Scholar : PubMed/NCBI
15	Kaestner KH, Knochel W and Martinez DE: Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev. 14:142–146. 2000.PubMed/NCBI
16	Chen H, Wang J, Yang H, Chen D and Li P: Association between FOXM1 and hedgehog signaling pathway in human cervical carcinoma by tissue microarray analysis. Oncol Lett. 12:2664–2673. 2016. View Article : Google Scholar : PubMed/NCBI
17	Wei P, Zhang N, Wang Y, Li D, Wang L, Sun X, Shen C, Yang Y, Zhou X and Du X: FOXM1 promotes lung adenocarcinoma invasion and metastasis by upregulating SNAIL. Int J Biol Sci. 11:186–198. 2015. View Article : Google Scholar : PubMed/NCBI
18	Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, Aldape KD, Xie TX, Pelloski CE, Xie K, et al: FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 66:3593–3602. 2006. View Article : Google Scholar : PubMed/NCBI
19	Major ML, Lepe R and Costa RH: Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators. Mol Cell Biol. 24:2649–2661. 2004. View Article : Google Scholar : PubMed/NCBI
20	Li Y, Zhang T, Zhang Y, Zhao X and Wang W: Targeting the FOXM1-regulated long noncoding RNA TUG1 in osteosarcoma. Cancer Sci. 109:3093–3104. 2018. View Article : Google Scholar : PubMed/NCBI
21	Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D, Wojewoda C, Miele L and Sarkar FH: Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells. J Cell Biochem. 112:78–88. 2011. View Article : Google Scholar : PubMed/NCBI
22	Miyashita A, Fukushima S, Nakahara S, Yamashita J, Tokuzumi A, Aoi J, Ichihara A, Kanemaru H, Jinnin M and Ihn H: Investigation of FOXM1 as a potential new target for Melanoma. PLoS One. 10:e01442412015. View Article : Google Scholar : PubMed/NCBI
23	Chen W, Yuan K, Tao ZZ and Xiao BK: Deletion of forkhead BoxM1 transcription factor reduces malignancy in laryngeal squamous carcinoma cells. Asian Pac J Cancer Prev. 12:1785–1788. 2011.PubMed/NCBI
24	Ahmad A, Wang Z, Kong D, Ali S, Li Y, Banerjee S, Ali R and Sarkar FH: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors. Breast Cancer Res Treat. 122:337–346. 2010. View Article : Google Scholar : PubMed/NCBI
25	Chen CH, Chien CY, Huang CC, Hwang CF, Chuang HC, Fang FM, Huang HY, Chen CM, Liu HL and Huang CY: Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity. Oncogene. 28:2723–2737. 2009. View Article : Google Scholar : PubMed/NCBI
26	Ma S, Pang C, Song L, Guo F and Sun H: Activating transcription factor 3 is overexpressed in human glioma and its knockdown in glioblastoma cells causes growth inhibition both in vitro and in vivo. Int J Mol Med. 35:1561–1573. 2015. View Article : Google Scholar : PubMed/NCBI
27	Ma Q, Zhou B and Zhang J: Expression and clinical significance of FoxM1 and Cep55 in basal-like breast cancer. Hebei Med J. 37:5–9. 2015.(In Chinese).
28	Chen L, Cao T, Li S, Luo L and Yang Y: Expression of FOXO3a in epithelial ovarian cancer and its correlation with clinicopathological features. Med J West China. 31:670–678. 2019.(In Chinese).
29	Chen GQ, Yao ZW and Luo X: Expression and clinical significance of FOXM1 in epithelial ovarian carcinoma. Life Sci Res. 15:70–74. 2011.(In Chinese).
30	Zhong Z, He ZW, Qiu Y, Ren NJ, Gao HB and Zhang K: Expression and corelation of MMP-2 and Ki-67 in human glioma tissues. Chin J Cancer Prev T Reat. 17:1070–1072. 2010.(In Chinese).
31	Shimizu Y, Segawa T, Inoue T, Shiraishi T, Yoshida T, Toa Y, Yamada T, Kinukawa N, Terada N, Kobayashi H, et al: Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men. BJU Int. 100:685–690. 2007. View Article : Google Scholar : PubMed/NCBI
32	Rychahou PG, Kang J, Gulhati P, Doan HQ, Chen LA, Xiao SY, Chung DH and Evers BM: Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci USA. 105:20315–20320. 2008. View Article : Google Scholar : PubMed/NCBI
33	Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH and Kalinichenko VV: The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 66:2153–2161. 2006. View Article : Google Scholar : PubMed/NCBI
34	Janus JR, Laborde RR, Greenberg AJ, Wang VW, Wei W, Trier A, Olsen SM, Moore EJ, Olsen KD and Smith DI: Linking expression of FOXM1,CEP55 and HELLS to tumorigenesis in oropharyngeal squamous cell carcinoma. Laryngoscope. 121:2598–2603. 2011. View Article : Google Scholar : PubMed/NCBI
35	Wen N, Wang Y, Wen L, Zhao SH, Ai ZH, Wang Y, Wu B, Lu HX, Yang H, Liu WC and Li Y: Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer. J Transl Med. 12:1342014. View Article : Google Scholar : PubMed/NCBI
36	Sullu Y, Demiraq GG, Yildirim A, Karaqoz F and Kandemir B: Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast. Pathol Res Pract. 207:747–753. 2011. View Article : Google Scholar : PubMed/NCBI
37	Coticchia CM, Curatolo AS, Zurakowski D, Yang J, Daniels KE, Matulonis UA and Moses MA: Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with normal CA125 levels. Gynecol Oncol. 123:295–300. 2011. View Article : Google Scholar : PubMed/NCBI
38	Peng WJ, Zhang JQ, Wang BX, Pan HF, Lu MM and Wang J: Prognostic value of matrix metalloproteinase 9 expression in patients with non-small cell lung cancer. Clin Chim Acta. 413:1121–1126. 2012. View Article : Google Scholar : PubMed/NCBI
39	Dai B, Kang SH, Gong W, Liu M, Aldape KD, Sawaya R and Huang S: Aberrant FoxM1B expression increases matrix metalloproteinase-2 transcription and enhances the invasion of glioma cells. Oncogene. 26:6212–6219. 2007. View Article : Google Scholar : PubMed/NCBI
40	Jiang C, Zhang Y, Li Y, Lu J, Huang Q, Xu R, Feng Y and Yan S: High CEP55 expression is associated with poor prognosis in non-small-cell lung cancer. Onco Targets Ther. 11:4979–4990. 2018. View Article : Google Scholar : PubMed/NCBI
41	Inoda S, Hirohashi Y, Torigoe T, Nakatsugawa M, Kiriyama K, Nakazawa E, Harada K, Takasu H, Tamura Y, Kamiguchi K, et al: Cep55/c10orf3, a tumor antigen derived from a centrosome residing protein in breast carcinoma. J Immunother. 32:474–485. 2009. View Article : Google Scholar : PubMed/NCBI
42	Coutant C, Rouzier R, Qi Y, Lehmann-Che J, Bianchini G, Lwamoto T, Hortobagyi GN, Symmans WF, Uzan S, Andre F, et al: Distinct p53 gene signatures are needed to predict prognosis and response to chemotherapy in ER-positive and ER-negative breast cancers. Clin Cancer Res. 17:2591–2601. 2011. View Article : Google Scholar : PubMed/NCBI
43	Dai J, Yang L, Wang J, Xiao Y and Ruan Q: Prognostic value of FOXM1 in patients with malignant solid tumor: A meta-analysis and system review. Dis Markers. 2015:3524782015. View Article : Google Scholar : PubMed/NCBI