BubR1 and AURKB overexpression are associated with a favorable prognosis in gastric cancer

Abstract

Abstract. The majority of human solid tumors exhibit aneuploidy caused by impairment of the mitotic checkpoint. Since the Mad2, Bubr1 and aurora kinase B (aurKB) proteins are involved in the mitotic checkpoint, we investigated Mad2, BubR1 and AURKB mrna expression and its effect on clinicopathological parameters and prognosis in 100 consecutive patients who underwent surgical resection for gastric cancer. Mad2, BubR1 and AURKB mrna expression levels in gastric cancer tissues and corresponding normal gastric mucosa were compared by real-time quantitative rT-Pcr. The data were then correlated to clinicopathological parameters and prognosis. The expression of Mad2, BubR1 and AURKB mrna was found to be significantly higher in cancer tissue compared to normal tissue. BubR1 and AURKB expression was significantly higher during the earlier stages of the disease. Patients with high BubR1 expression had improved relapse-free survival and overall survival compared to patients with low BubR1 expression. Multivariate analysis of stage ii and iii patients indicated that high expression of BubR1 and/or AURKB was associated with improved overall survival. We conclude that overexpression of BubR1 and AURKB is associated with a low risk of gastric cancer progression, and that overexpression of BubR1 and/or AURKB can therefore be used to identify gastric cancer patients with a favorable prognosis. Introductiondespite the declining incidence of gastric cancer, the disease remains the fourth most common cancer and the second most frequent cause of cancer-related death worldwide (1,2). recent progress in diagnostic and treatment technologies has improved the long-term survival of patients with earlystage gastric cancer, although the prognosis for patients with advanced disease remains unfavorable (3). Surgical treatment is the mainstay of therapy for patients with localized disease, but adjuvant chemotherapy is required after surgical resection in advanced cases (4). Thus, the identification of prognostic factors may contribute to improved treatment strategies for gastric cancer patients. This requires further insight into carcinogenesis and cancer progression.The majority of human solid tumors exhibit aneuploidy (5), which is a very early event in the progression of gastric cancer (6). Tumor cells become aneuploid as a result of aberrant mitotic division, caused by a defective mitotic checkpoint response. The mitotic checkpoint is a signaling cascade that arrests the cell cycle in mitosis when even a single chromosome is not properly attached to the mitotic spindle (5,7).The mitotic checkpoint complex contains the anaphasepromoting complex/cyclosome activator cdc20, as well as mitotic checkpoint kinases (McKs) such as Mad2 (mitotic arrest deficient-like 1; MAD2L1), BubR1 (budding uninhibited by benzimidazoles 1 homolog ß; BUB1B) and Bub3. The McKs are regarded as effectors of the mitotic checkpoint. Within the McK complex, both Mad2 and Bubr1 directly bind cdc20 (8). a large number of aneuploid cell lines do not appear to harbor mut...

Immunohistochemical expression of budding uninhibited by benzimidazole related 1 in leukoplakia and oral squamous cell carcinoma

“…Various factors appear to play a role in aneuploidy which includes sister chromatid cohesion, abnormal kinetochore structure, mitotic checkpoint dysfunction or centrosome abnormalities. [ 13 ] Impaired SAC function has also been suggested to be one of the common causes of aneuploidy in human cancers. [ 14 ]…”

“…[ 7 ] This aberrant expression plays a significant role in cancer initiation and progression. [ 13 ] Its expression is considered as a marker for poor survival in certain types of human cancer. [ 6 ] Mutation of hBUB1B gene appears to be a rare event in human malignancy supporting the view that BUBR1 overexpression is as a result of up-regulation of the normal gene.…”

Genetic Aspects of Gastric Cancer Instability

“…Ando et al, on the other hand, found a significant high correlation between BUBR1 overexpression and DNA aneuploidy [37]. Interestingly, in another study investigating the expression status of BUBR1 and AURKB, the authors concluded that overexpression of BubR1 and AURKB is associated with a low risk of gastric cancer progression [38]. MAD1 and MAD2 are also important regulators of cell cycle progression, involved in alignment of chromosomes at the metaphase plate.…”

Identification of differentially expressed genes in the development of osteosarcoma using RNA-seq

“…Up-regulation of AURKB in Epstein-Barr virus- (EBV)-transformed lymphoblasts is correlated with EBV immortalization and tumorigenic ability in vitro [12]. A number of studies discover that high expression of AURKB is associated with unfavorable prognosis of cancers such as acute myeloid leukemia, nasopharyngeal carcinoma, colorectal adenocarcinoma and gastric cancer [13–16]. Suppression of AURKB down-regulates phosphorylation of VCP and activates the NF-κB signaling pathway in OS cells, resulting in inhibition of cell proliferation, migration and invasion [17].…”