Elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma

Abstract

Astrocytoma is the most common type of primary malignant brain tumor, with pretty lowly 5-year survival rate in patients. Although extended surgical removal of the tumor and postoperative chemotherapy/radiotherapy executed, still there is large recurrence rate, mainly because diffuse glioma tumor cells ubiquitously infiltrate into normal parenchyma. So it becomes a priority to hunt novel molecular and signaling pathway targets to suppress astrocyma progression. HSP10, an important member of Heat shock proteins (Hsps) family, classically works as molecular chaperone folding or degradating of target proteins. Evolutionarily, HSP10 is also reported to be involved in immunomodulation and tumor progression. Poly (ADP-ribose) polymerase (PARP), important in DNA repair, is one of the main cleavage targets of caspase. And cleaved PARP (c-PARP) can serve as a marker of cells undergoing apoptosis. So far, whether the expression of HSP10 or c-PARP is associated with clinicopathologic implication for astrocytoma has not been reported. Meanwhile, it is unclear about the relationship between HSP10 and cell apoptosis. The purpose of this research is to elucidate the association between the expression of HSP10 and c-PARP and clinicopathological characteristics of astrocytoma by immunohistochemistry. The results showed that positive percentage of high HSP10 expression in astrocytoma 42/103, 40.8%) was significantly higher than that in the non-tumor control brain tissues (8/43, 18.6%) (P = 0.01). While no apparent difference of high c-PARP expression existed between astrocytoma and non-tumor control brain tissues. Furthermore, elevated expression of HSP10 was negative related to low expression of c-PARP (r = -0.224, P = 0.023), indicating high expression of HSP10 in astrocytoma inhibited apoptosis process effectively. And overexpression of HSP10 was proved to be the independent poor prognostic factor for astrocytoma by multivariate analysis. Taken together, our results suggest that elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma.

Fig 1. Expression of HSP10 and c-PARP proteins in astrocytoma was detected by immunohistochemistry.

1-A, B: Positive expression of HSP10 was located in the cytoplasm of astrocytoma cells (high expression) and non-tumor control brain tissues (low expression) (20x, IHC, DAB staining). 1-C, D: Positive staining of c-PARP (arrows) was identified in the nucleus of astrocytoma cells (low expression: low apoptotic indices, AIs) and in the neurons of non-tumor control brain tissues (high expression: high AIs) (20x, IHC, DAB staining).

Fig 2. Expression of HSP10 and c-PARP proteins in astrocytoma compared to non-tumor control brain tissues.

Results showed that there were significant differences between the groups which were statistically evaluated by chi-square test (P < 0.05).

Fig 3. Kaplan-Meier curves according to expression of HSP10 and c-PARP proteins and common expression of two proteins divided into high and low expression.

A: High expression of HSP10 was significantly correlated to poor prognosis of astrocytoma patients (P = 0.001, two sided). B: High expression of c-PARP did not significantly relate with survival of astrocytoma patients (P = 0.650, two sided). C: Astrocytoma patients with high expression of HSP10 and low expression of c-PARP had significantly short survival times (P < 0.019, two sided). D: Astrocytoma patients with high pathologic grades were evidently poor overall survival (P< 0.001, two sided).