High ATP2A2 expression correlates with better prognosis of diffuse astrocytic tumor patients.
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.
Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Wei-Qing
WQ
Li
Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Nan-Zhe
NZ
Zhong
Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Jin
J
He
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Yi-Ming
YM
Li
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Li-Jun
LJ
Hou
Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Hui-Min
HM
Liu
Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Chun-Yan
CY
Xia
Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Liang-Zhe
LZ
Wang
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Yi-Cheng
YC
Lu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002648:Child; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009368:Neoplasm Transplantation; D011379:Prognosis; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation; D055815:Young Adult
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human