Chromatin-regulating genes are associated with postoperative prognosis and isocitrate dehydrogenase mutation in astrocytoma

Abstract

Background: Abnormality in chromatin regulation is a major determinant in the progression of multiple neoplasms. Astrocytoma is a malignant histologic morphology of glioma that is commonly accompanied by chromatin dysregulation. However, the systemic interpretation of the expression characteristics of chromatin-regulating genes in astrocytoma is unclear.Methods: In this study, we investigated the expression profile of chromatin regulation genes in 194 astrocytoma patients sourced from The Cancer Genome Atlas (TCGA) database. The relevance of gene expression and postoperative survival outcomes was assessed.Results: Based on the expression patterns of chromatin regulation genes, two primary clusters and three subclusters with significantly different survival outcomes were identified. The patients in cluster_1 (or subcluster_1) had a poorer prognosis than the other groups, and this particular cohort were older, with a more advanced grade of tumor and isocitrate dehydrogenase-wildtype distribution. Detection of the differentially expressed genes revealed that the group with poor prognosis was characterized by downregulation of H2AFY2, WAC, HDAC5, ZMYND11, TET1, SATB1, and MYST4, and overexpression of EYA4. Moreover, all eight genes were significantly correlated with overall survival (OS) in astrocytoma.Age-associated genes were investigated and the expression levels of EYA4, TET1, SATB1, WAC, ZMYND11, and H2AFY2 were found to be closely correlated with advanced age. Regression analysis suggested that the expression levels of H2AFY2, HILS1, EYA1, EYA4, and KDM5B were independently associated with IDH mutation status. The differential expressions of 34 common genes were significantly associated with age, grade, and IDH mutant. Conclusions:The study revealed that the expression pattern of chromatin regulation genes was significantly associated with postoperative prognosis in astrocytoma. Moreover, the differential expression of particular genes was strongly associated with clinical characteristics such as age, grade, and IDH subtype. These results suggest that the genes involved in chromatin regulation play important roles in the biological process of astrocytoma progression, and these molecules could potentially serve as therapeutic targets in astrocytoma.

The Role of MacroH2A Histone Variants in Cancer

“…Reduced expression of macroH2A-encoding genes was observed in highly proliferating tumors of various origins [82] including melanoma [107]. Prognostically, low expression of macroH2A1.1 and macroH2A2 is associated with poor prognosis in several cancers such as lung, colorectal and breast cancer and astrocytoma [108][109][110][111]. The mechanistic causes for downregulation of macroH2A expression have been investigated in myelodysplastic syndrome (MDS), a bone marrow failure disorder characterized by defects in hematopoietic differentiation that eventually may progress to acute myeloid leukemia (AML) [112].…”

The Effect of Necroptosis-related Gene Signature on the Progression, Prognosis, and Immune Microenvironment of Low-grade Glioma

“…The BID gene is also one of our prognostic model markers [35]. Kun Zhang found that H2AFY2 is a poor prognostic gene in gliomas [36]. MAPK9 is upregulated in normal tissues.…”

High HDAC5 expression correlates with a poor prognosis and the tumor immune microenvironment in gastric cancer

“…The expressions of HDACs in GC have also been investigated, and some studies have reported that the expression levels of HDAC1, HDAC2, and HDAC4 are upregulated in cancer tissues (25)(26)(27), while some other family members, such as HDAC3, have been shown to exhibit decreased expression in cancer tissues (28). However, studies on HDAC5 in GC are lacking, and the results of available studies are highly variable; therefore, investigated HDAC5 in astrocytoma and found that HDAC5 expressed at high levels was indicative of a better prognosis (33), suggesting that this gene exhibits different prognostic values for different cancer types. There are few studies on the prognosis of HDAC5 in GC patients, and only Chen et al have studied the effect of HDAC5 on the prognosis of GC; their study confirmed that a high HDAC5 expression level was closely associated with poor prognosis (30).…”

“…Similarly, Klieser et al ’s study in pNET confirmed HDAC5 as a predictor of poor clinical outcomes ( 9 ). However, Zhang et al investigated HDAC5 in astrocytoma and found that HDAC5 expressed at high levels was indicative of a better prognosis ( 33 ), suggesting that this gene exhibits different prognostic values for different cancer types. There are few studies on the prognosis of HDAC5 in GC patients, and only Chen et al have studied the effect of HDAC5 on the prognosis of GC; their study confirmed that a high HDAC5 expression level was closely associated with poor prognosis ( 30 ).…”