Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication

Begnami, María Dirlei; Fregnani, José Humberto Tavares Guerreiro; Nonogaki, Suely; Soares, Fernando Augusto

doi:10.1016/j.humpath.2010.01.007

Cited by 60 publications

(56 citation statements)

References 33 publications

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“…This means that CCNB1 expression value maybe have the potential to be a biomarker in the diagnosis of GC. Moreover, high levels of CCNB1 also indicate lymph node metastasis and poor prognosis in GC (Begnami et al, 2010). Thus, CCNB1 may be a potential biomarker in the diagnosis and prognosis of GC.…”

Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

Wang

Chen²,

Wen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.

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Section: Discussionmentioning

confidence: 99%

Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

Wang

Chen²,

Wen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…One of the checkpoints, the G2/M checkpoint blocks the entry into mitosis when DNA is damaged. Cyclin B1 and CDK1 are essential for G2/M phase transitions of eukaryotic cell cycle [35-37]. ISG15 knockdown can reduce the expression of Cyclin B1 and CDK1 and induce G2/M phase cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

Interferon-stimulated Gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma

Zhang

et al. 2014

Oncotarget

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with poor prognosis. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. However, the role of ISG15 in HCC remains unclear. In this study, we investigated the function of ISG15 during HCC progression and related mechanism using clinicopathological data, cell line and xenograft model. Our results indicated that ISG15 is highly expressed in HCC tissues and multiple HCC cell lines. ISG15 expression is significantly associated with the differentiation grade, metastatic of tumor and survival of HCC patients. However, the expression of ISG15 is not affected by HBV infection. ISG15 promotes the proliferation and migration of hepatocarcinoma cells through maintaining Survivin protein stabilization via sequestering XIAP from interacting with Survivin. Knowing down ISG15 with SiRNA inhibited the xenografted tumor growth and prolonged the lifespan of tumor-bearing mice. All these results support that ISG15 high expression is an intrinsic feature for HCC and a trigger for tumorigenesis and metastasis. ISG15 may be a prognostic biomarker and the inhibition of ISG15 could provide a therapeutic advantage for HCC patients over-expressing ISG15.

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“…Furthermore, recent studies have indicated associations between promoter hypermethylation of the ATM gene and reduced postoperative survival in head and neck squamous cell carcinoma, non-small cell lung cancer, and breast cancer [17], and another study reported that the expressional loss of ATM was associated with poor prognosis in colorectal cancer [18]. In ovarian cancer, although ATM and Chk2 protein expressions were not found to be individually related to overall survival, at least one alteration was found to be a negative predictor of overall survival [19].…”

Section: Discussionmentioning

confidence: 99%

DNA Damage Response-Related Proteins in Gastric Cancer: ATM, Chk2 and p53 Expression and Their Prognostic Value

et al. 2013

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Objectives: The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma. Methods: Two independent cohorts, a training set (n = 524) and validation set (n = 394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions were examined by immunohistochemistry using tissue microarray. Results: ATM loss, Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively. In the training set, the aberrant expressions of ATM, Chk2, or p53 were significantly associated with an advanced TNM stage and poor disease-specific survival. This association was verified in the validation set. Chk2 positivity and p53 negativity were significantly related to a prolonged disease-specific survival. Also, patients with nonaberrant expressional levels of all 3 DDR-related proteins had a more favorable outcome than others. Multivariate analyses showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as independent prognostic factors of poor disease-specific survival. Conclusions: This study elucidated the prognostic implications of DDR-related proteins, and suggests that their aberrant expressions play critical roles in the development and progression of gastric cancer.

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Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication

Cited by 60 publications

References 33 publications

Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

Interferon-stimulated Gene 15 (ISG15) is a trigger for tumorigenesis and metastasis of hepatocellular carcinoma

DNA Damage Response-Related Proteins in Gastric Cancer: ATM, Chk2 and p53 Expression and Their Prognostic Value

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