CDC20 with malignant progression and poor prognosis of astrocytoma revealed by analysis on gene expression

Abstract

The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test. Candidate genes were screened by DAVID and Kaplan-Meier survival analysis. Further, the significant candidate genes were validated through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in different grades of glioma. Finally, the association of target gene and clinical molecular characterization was analyzed by Chi-squared analysis. The cell-division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p = 0.0046) were screened by statistical and Kaplan-Meier survival analysis. The expression levels of CDC20 and PLK1 rose significantly through real-time PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with CDC20 high-expression differ from patients with CDC20 low-expression in terms of WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001), isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein amplification (EGFR, p = 0.048). Moreover, the biological processes analyses indicate CDC20 might have an essential role in astrocyte cell proliferation. We demonstrated that the expression level of CDC20 increases significantly along with malignant progression and poor prognosis of astrocytoma.

CDC20 associated with cancer metastasis and novel mushroom‑derived CDC20 inhibitors with antimetastatic activity

“…Cell migration of the PANC-1 cells treated with PTE (30 and 60 µg/ml) or PPAC (30 and 60 µM) was assessed in Transwell chambers according to an established method (29). The PANC-1 cells (0.2x10 6 ) suspended in serum-free medium were added to the upper chamber of an insert, and the insert was placed in a 24-well plate containing medium with 10% FBS. The migration assays were performed for 24 h at 37˚C.…”

“…It activates the anaphase-promoting complex/cyclosome, thus modulating mitotic exit through the proteasomal degradation of proteins (2)(3)(4). Aberrant expression of CDC20 is associated with malignant progression and poor prognosis in various types of cancer, including pancreatic ductal adenocarcinoma, gastric cancer, urothelial bladder cancer, astrocytoma, hepatocellular carcinoma, lung adenocarcinoma and oral squamous cell carcinoma (5)(6)(7)(8)(9)(10)(11). In addition, there is a significant correlation between a high expression of CDC20 and advanced tumor stage in carcinoma of the breast, colon, endometrium and prostate (12)(13)(14).…”

Multivariate analysis reveals differentially expressed genes among distinct subtypes of diffuse astrocytic gliomas: diagnostic implications

“…The latter tumors were further divided on histopathological grounds into three grades of malignancy associated with distinct median survival rates (range: from 1 to > 10 years) 5,6 : WHO grade-II diffuse astrocytoma (DA), WHO grade-III anaplastic astrocytoma (AA) and WHO grade-IV glioblastoma (GBM). Of note, DA might evolve to AA, and AA might transform to GBM 7,8 . Because of this, GBM is further subdivided into primary de novo GBM (pGBM) and secondary GBM (sGBM) resulting from progression of a prior lower grade astrocytic tumor (e.g.…”

“…Because of this, GBM is further subdivided into primary de novo GBM (pGBM) and secondary GBM (sGBM) resulting from progression of a prior lower grade astrocytic tumor (e.g. AA) 7 .…”

Hyperphosphorylation of CDH1 in Glioblastoma Cancer Stem Cells Attenuates APC/CCDH1 Activity and Pharmacologic Inhibition of APC/CCDH1/CDC20 Compromises Viability

“…Our study also highlights the utility of small-molecule inhibition of APC/C CDH1/CDC20 as a therapeutic strategy to target CSCs in GBM. Elevated CDC20 expression has previously been correlated with high grade glioma, as well as poor patient prognosis by a number of groups (54)(55)(56)(57). We and others have shown that CDC20 is higher in CSCs over NSTCs and, more recently, RNAi has validated CDC20 as a critical modulator of the CSC phenotype (13)(14)(15).…”