High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients

Li,Wei-Qing; Zhong,Nan-Zhe; He,Jin; Li,Yi-Ming; Hou,Li-Jun; Liu,Hui-Min; Xia,Chun-Yan; Wang,Liang-Zhe; Lu,Yi-Cheng

doi:10.3892/or.2017.5528

High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients

Authors:
- Wei-Qing Li
- Nan-Zhe Zhong
- Jin He
- Yi-Ming Li
- Li-Jun Hou
- Hui-Min Liu
- Chun-Yan Xia
- Liang-Zhe Wang
- Yi-Cheng Lu
View Affiliations

Affiliations: Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
Published online on: March 24, 2017 https://doi.org/10.3892/or.2017.5528
Pages: 2865-2874

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Novel molecular markers are required for defining subsets of diffuse astrocytic tumor patients with differing prognoses. Here, we examined ATP2A2 expression in 109 human diffuse astrocytic tumor samples (39 grade II diffuse astrocytoma (DA), 19 grade III anaplastic astrocytoma (AA), 51 grade IV glioblastoma) and its correlation with patient clinicopathologic characteristics. ATP2A2 expression significantly correlated with tumor grade and survival (P<0.05). High ATP2A2 expression was detected in 35.3% (18/51) of glioblastoma patients, compared to 61.5% (24/39) in grade II, and 52.6% (10/19) in grade III astrocytoma patients (P=0.043). The median survival was 45±5.3 (95% CI, 34.7-55.3) months in patients with high ATP2A2 expression and 16±5.0 (95% CI, 6.3-25.7) months in patients with low ATP2A2 expression (P<0.0001). Additionally, high grade astrocytoma patients with high ATP2A2 expression showed longer survival (median, 31.0±4.9 months, 95% CI, 21.4-40.7) than those with low ATP2A2 expression (median: 13.0±1.6 months, 95% CI, 9.9-16.1; P=0.027). Furthermore, both ATP2A2 overexpression and IDH1 mutation were detected in secondary glioblastoma, AA developed from DA and oligodendrogiomas with IDH1 mutation. The MTT assays showed that lentiviral ATP2A2 overexpression significantly suppressed the clonogenic growth of glioblastoma U251MG cells (P<0.05). Xenografts stably overexpressing ATP2A2 were markedly smaller in size 4 weeks post inoculation (P<0.05). Our findings identified high ATP2A2 expression in a subset of astrocytoma patients that was associated with better prognosis and ATP2A2 suppressed astrocytoma growth.

View Figures

View References

1	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
2	Parisot S, Darlix A, Baumann C, Zouaoui S, Yordanova Y, Blonski M, Rigau V, Chemouny S, Taillandier L, Bauchet L, et al: A probabilistic atlas of diffuse WHO grade II glioma locations in the brain. PLoS One. 11:e01442002016. View Article : Google Scholar : PubMed/NCBI
3	Dubrow R, Darefsky AS, Jacobs DI, Park LS, Rose MG, Laurans MS and King JT Jr: Time trends in glioblastoma multiforme survival: The role of temozolomide. Neuro-oncol. 15:1750–1761. 2013. View Article : Google Scholar : PubMed/NCBI
4	Mesti T and Ocvirk J: Malignant gliomas: Old and new systemic treatment approaches. Radiol Oncol. 50:129–138. 2016.PubMed/NCBI
5	Watanabe T, Nobusawa S, Kleihues P and Ohgaki H: IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol. 174:1149–1153. 2009. View Article : Google Scholar : PubMed/NCBI
6	Chow LM, Endersby R, Zhu X, Rankin S, Qu C, Zhang J, Broniscer A, Ellison DW and Baker SJ: Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain. Cancer Cell. 19:305–316. 2011. View Article : Google Scholar : PubMed/NCBI
7	Hofer S, Rushing E, Preusser M and Marosi C: Molecular biology of high-grade gliomas: What should the clinician know? Chin J Cancer. 33:4–7. 2014. View Article : Google Scholar : PubMed/NCBI
8	Bchetnia M, Benmously R, Ben Brick AS, Charfeddine C, Ben Ameur Y, Fajraoui M, Debbiche A, Ben Ayed M, Mokni M, Fenniche S, et al: New mutations of Darier disease in Tunisian patients. Arch Dermatol Res. 301:615–619. 2009. View Article : Google Scholar : PubMed/NCBI
9	Shi BJ, Feng J, Ma CC, Yan XN, Li WB, Wei YP, Hu G and Wang XL: Novel mutations of the ATP2A2 gene in two families with Darier's disease. Arch Dermatol Res. 301:27–30. 2009. View Article : Google Scholar : PubMed/NCBI
10	Papp B, Brouland JP, Gélébart P, Kovàcs T and Chomienne C: Endoplasmic reticulum calcium transport ATPase expression during differentiation of colon cancer and leukaemia cells. Biochem Biophys Res Commun. 322:1223–1236. 2004. View Article : Google Scholar : PubMed/NCBI
11	Wu Y, Palad AJ, Wasilenko WJ, Blackmore PF, Pincus WA, Schechter GL, Spoonster JR, Kohn EC and Somers KD: Inhibition of head and neck squamous cell carcinoma growth and invasion by the calcium influx inhibitor carboxyamido-triazole. Clin Cancer Res. 3:1915–1921. 1997.PubMed/NCBI
12	Baron S, Vangheluwe P, Sepúlveda MR, Wuytack F, Raeymaekers L and Vanoevelen J: The secretory pathway Ca (2+)-ATPase 1 is associated with cholesterol-rich microdomains of human colon adenocarcinoma cells. Biochim Biophys Acta. 1798:1512–1521. 2010. View Article : Google Scholar : PubMed/NCBI
13	Matsui K, Makino T, Nakano H, Furuichi M, Sawamura D and Shimizu T: Squamous cell carcinoma arising from Darier's disease. Clin Exp Dermatol. 34:e1015–e1016. 2009. View Article : Google Scholar : PubMed/NCBI
14	Bleeker NP, Cornea RL, Thomas DD and Xing C: A novel SERCA inhibitor demonstrates synergy with classic SERCA inhibitors and targets multidrug-resistant AML. Mol Pharm. 10:4358–4366. 2013. View Article : Google Scholar : PubMed/NCBI
15	Wang L, Li W, Yang Y, Hu Y, Gu Y, Shu Y, Sun Y, Wu X, Shen Y and Xu Q: High expression of sarcoplasmic/endoplasmic reticulum Ca (2+)-ATPase 2b blocks cell differentiation in human liposarcoma cells. Life Sci. 99:37–43. 2014. View Article : Google Scholar : PubMed/NCBI
16	Prasad V, Boivin GP, Miller ML, Liu LH, Erwin CR, Warner BW and Shull GE: Haploinsufficiency of Atp2a2, encoding the sarco (endo)plasmic reticulum Ca²⁺-ATPase isoform 2 Ca²⁺ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. Cancer Res. 65:8655–8661. 2005. View Article : Google Scholar : PubMed/NCBI
17	Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 455:1061–1068. 2008. View Article : Google Scholar : PubMed/NCBI
18	Yoshiki S, Matsunaga-Udagawa R, Aoki K, Kamioka Y, Kiyokawa E and Matsuda M: Ras and calcium signaling pathways converge at Raf1 via the Shoc2 scaffold protein. Mol Biol Cell. 21:1088–1096. 2010. View Article : Google Scholar : PubMed/NCBI
19	Sorrentino G, Comel A and Del Sal G: p53 orchestrates calcium signaling in vivo. Cell Cycle. 14:1343–1344. 2015. View Article : Google Scholar : PubMed/NCBI
20	Takuwa N, Zhou W, Kumada M and Takuwa Y: Ca (2+)-dependent stimulation of retinoblastoma gene product phosphorylation and p34cdc2 kinase activation in serum-stimulated human fibroblasts. J Biol Chem. 268:138–145. 1993.PubMed/NCBI
21	Rasmussen CD and Means AR: Calmodulin is required for cell-cycle progression during G1 and mitosis. EMBO J. 8:73–82. 1989.PubMed/NCBI
22	Korosec B, Glavac D, Rott T and Ravnik-Glavac M: Alterations in the ATP2A2 gene in correlation with colon and lung cancer. Cancer Genet Cytogenet. 171:105–111. 2006. View Article : Google Scholar : PubMed/NCBI
23	Korosec B, Glavac D, Volavsek M and Ravnik-Glavac M: Alterations in genes encoding sarcoplasmic-endoplasmic reticulum Ca (2+) pumps in association with head and neck squamous cell carcinoma. Cancer Genet Cytogenet. 181:112–118. 2008. View Article : Google Scholar : PubMed/NCBI
24	Huang MY, Wang HM, Tok TS, Chang HJ, Chang MS, Cheng TL, Wang JY and Lin SR: EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 as potential prognostic markers for postoperative Taiwanese colorectal cancer patients. DNA Cell Biol. 31:625–635. 2012. View Article : Google Scholar : PubMed/NCBI
25	Legrand G, Humez S, Slomianny C, Dewailly E, Vanden Abeele F, Mariot P, Wuytack F and Prevarskaya N: Ca²⁺ pools and cell growth. Evidence for sarcoendoplasmic Ca²⁺-ATPases 2B involvement in human prostate cancer cell growth control. J Biol Chem. 276:47608–47614. 2001. View Article : Google Scholar : PubMed/NCBI
26	Karsy M, Neil JA, Guan J, Mahan MA, Colman H and Jensen RL: A practical review of prognostic correlations of molecular biomarkers in glioblastoma. Neurosurg Focus. 38:E42015. View Article : Google Scholar : PubMed/NCBI
27	Reitman ZJ, Duncan CG, Poteet E, Winters A, Yan LJ, Gooden DM, Spasojevic I, Boros LG, Yang SH and Yan H: Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia. J Biol Chem. 289:23318–23328. 2014. View Article : Google Scholar : PubMed/NCBI
28	Flores-Peredo L, Rodríguez G and Zarain-Herzberg A: Induction of cell differentiation activates transcription of the Sarco/Endoplasmic Reticulum calcium-ATPase 3 gene (ATP2A3) in gastric and colon cancer cells. Mol Carcinog. 56:735–750. 2017. View Article : Google Scholar : PubMed/NCBI
29	Arbabian A, Brouland JP, Apáti Á, Pászty K, Hegedűs L, Enyedi Á, Chomienne C and Papp B: Modulation of endoplasmic reticulum calcium pump expression during lung cancer cell differentiation. FEBS J. 280:5408–5418. 2013. View Article : Google Scholar : PubMed/NCBI
30	Berridge MJ, Bootman MD and Roderick HL: Calcium signalling: Dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 4:517–529. 2003. View Article : Google Scholar : PubMed/NCBI
31	Monteith GR, McAndrew D, Faddy HM and Roberts-Thomson SJ: Calcium and cancer: Targeting Ca²⁺ transport. Nat Rev Cancer. 7:519–530. 2007. View Article : Google Scholar : PubMed/NCBI
32	Johnson GG, White MC and Grimaldi M: Stressed to death: Targeting endoplasmic reticulum stress response induced apoptosis in gliomas. Curr Pharm Des. 17:284–292. 2011. View Article : Google Scholar : PubMed/NCBI
33	Das A, Banik NL and Ray SK: Flavonoids activated caspases for apoptosis in human glioblastoma T98G and U87MG cells but not in human normal astrocytes. Cancer. 116:164–176. 2010.PubMed/NCBI
34	Kovacs GG, Zsembery A, Anderson SJ, Komlosi P, Gillespie GY, Bell PD, Benos DJ and Fuller CM: Changes in intracellular Ca²⁺ and pH in response to thapsigargin in human glioblastoma cells and normal astrocytes. Am J Physiol Cell Physiol. 289:C361–C371. 2005. View Article : Google Scholar : PubMed/NCBI
35	Seo JA, Kim B, Dhanasekaran DN, Tsang BK and Song YS: Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca²⁺ ATPase activity in ovarian cancer cells. Cancer Lett. 371:30–37. 2016. View Article : Google Scholar : PubMed/NCBI