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

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.

Altered SERCA Expression in Breast Cancer

“…The sarco/endoplasmic reticulum (SR/ER) Ca 2+ ATPase pump (SERCA) belongs to the P-type pump family, which includes a large number of evolutionarily related Ca 2+ pumps. There are three SERCA ATPase SR/ER Ca 2+ -transporting (ATP2A)1-3 eukaryotic genes that exist, which encode for 14 isoforms with tissue-specific expression profiles [ 7 , 8 , 9 , 10 ]. All of the isoforms have 75% homology and are cell-type-dependent [ 11 ].…”

“…Conversely, reduced ATP2A2 expression levels due to alterations in gene-promoter activity have been found in patient tissue biopsies and may be an early event in tumorigenesis [ 7 ]. Additionally, ATP2A2 expression levels are significantly correlated with tumor grade and survival rates, where high ATP2A2 expression has been detected in patients with glioblastoma [ 9 ]. In a separate study, ATP2A3 gene downregulation has been reported in gastric and colon cancer types.…”

LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia

“…Subsequently, we verified that LINC00221 posed anti-proliferation and pro-apoptosis effects on ALL cells via down-regulating ATP2A2. High expression of ATP2A2 was identified to be positively correlated with favorable prognosis of astrocytoma [24].…”

Lentiviral Vectors as Tools for the Study and Treatment of Glioblastoma

“…Identified mechanisms giving reason of this result were the induction of apoptosis and cell differentiation accompanied by a down-regulation of the Wnt/beta-catenin signaling pathway [28]. Furthermore, LV-mediated overexpression led to the identification of the SERCA Ca2 + -ATPase ATP2A2 as a beneficial factor for survival [29].…”