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http://dx.doi.org/10.7314/APJCP.2012.13.7.3437

The Clinicopathological Significance of Bmi-1 Expression in Pathogenesis and Progression of Gastric Carcinomas  

Lu, Hang (Department of General Surgery, First Affiliated Hospital of Liaoning Medical University)
Sun, Hong-Zhi (Department of General Surgery, First Affiliated Hospital of Liaoning Medical University)
Li, Hua (Department of Oncology, First Affiliated Hospital of Liaoning Medical University)
Cong, Ming (Department of Neurological Surgery, First Affiliated Hospital of Liaoning Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.7, 2012 , pp. 3437-3441 More about this Journal
Abstract
Background: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an important role in the regulation of proliferation, senescence, cell cycle and apoptosis, chromosome stability, activation of gene transcription. Methods: To clarify the roles of Bmi-1 in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a comparison of its expression with clinicopathological parameters of carcinomas. Results: There was gradually increased Bmi-1 protein expression from gastritis, IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to tumor size, depth of invasion, lymph node metastasis and worse prognosis of carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse-type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was observed in gastric carcinoma with larger diameter, deeper invasion, lymph node metastasis, and intestinal-type carcinoma (p<0.05). Conclusion: These findings indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviors and prognosis of gastric carcinomas.
Keywords
Bmi-1; gastric carcinoma; pathogenesis; progression; prognosis;
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1 Guo BH, Feng Y, Zhang R, et al (2010). Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer. Mol Cancer, 10, 10.
2 Engelsen IB, Mannelqvist M, Stefansson IM, et al (2008). Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma. Br J Cancer, 98, 1662-9.   DOI
3 Grinstein E, Mahotka C. Stem cell divisions controlled by the proto-oncogene BMI-1. J Stem Cells, 4, 141-6.
4 Jiang L, Li J, Song L (2009). Bmi-1, stem cells and cancer. Acta Biochim Biophys Sin (Shanghai), 41, 527-34.   DOI
5 Xiao J, Deng C (2009). Knockdown of Bmi-1 impairs growth and invasiveness of human gastric carcinoma cells. Oncol Res, 17, 613-20.   DOI
6 Song W, Tao K, Li H et al (2010). Bmi-1 is related to proliferation, survival and poor prognosis in pancreatic cancer. Cancer Sci, 101, 1754-60.   DOI
7 Wang JF, Liu Y, Liu WJ, He SY (2010). Expression of Bmi-1 gene in esophageal carcinoma cell EC9706 and its effect on cell cycle, apoptosis and migration. Chin J Cancer, 29, 689-96.   DOI
8 Wang Y, Zhe H, Ding Z, et al (2012). Cancer stem cell marker Bmi-1 expression is associated with basal-like phenotype and poor survival in breast cancer. World J Surg, 36, 1189-94.   DOI
9 Xu Z, Liu H, Lv X, et al (2011). Knockdown of the Bmi-1 oncogene inhibits cell proliferation and induces cell apoptosis and is involved in the decrease of Akt phosphorylation in the human breast carcinoma cell line MCF-7. Oncol Rep, 25, 409-18.
10 Hayry V, Makinen LK, Atula T, et al (2010). Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue. Br J Cancer, 102, 892-7.   DOI
11 Honig A, Weidler C, Hausler S, et al (2010). Overexpression of polycomb protein BMI-1 in human specimens of breast, ovarian, endometrial and cervical cancer. Anticancer Res, 30, 1559-64.
12 Zhang X, Wang C, Wang L, et al (2012). Detection of circulating Bmi-1 mRNA in plasma and its potential diagnostic and prognostic value for uterine cervical cancer. Int J Cancer, 131, 165-72.   DOI
13 Yang GF, He WP, Cai MY, et al (2010). Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma. BMC Cancer, 10, 133.   DOI
14 Yin T, Wei H, Leng Z, et al (2011). Bmi-1 promotes the chemoresistance, invasion and tumorigenesis of pancreatic cancer cells. Chemotherapy, 57, 488-96.   DOI
15 Yu M, Zheng HC, Xia P, et al (2010). Comparison in pathological behaviours & prognosis of gastric cancers from general hospitals between China & Japan. Indian J Med Res, 132, 295-302.
16 Zhang X, Wang CX, Zhu CB, et al (2010). Overexpression of Bmi-1 in uterine cervical cancer: correlation with clinicopathology and prognosis. Int J Gynecol Cancer, 20, 1597-603.
17 Zhang YC (1994). Geographic pathology of gastric dysplasia in China. Semin Surg Oncol, 10, 100-6.   DOI
18 Zheng H, Takahashi H, Murai Y, et al (2007). Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan: an immunostaining study on the tissue microarray. J Clin Pathol, 60, 273-7.
19 Huber GF, Albinger-Hegyi A, Soltermann A, et al (2010). Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma. Cancer in press.
20 Huang J, Qiu Y, Chen G, Huang L, He J (2011). The relationship between Bmi-1 and the epithelial-mesenchymal transition in lung squamous cell carcinoma. Med Oncol, [Epub ahead of print] PubMed
21 Itahana K, Zou Y, Itahana Y, et al (2003). Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1. Mol Cell Biol, 23, 389-401.   DOI
22 Min L, Dong-Xiang S, Xiao-Tong G, Ting G, Xiao-Dong C (2011). Clinicopathological and prognostic significance of Bmi-1 expression in human cervical cancer. Acta Obstet Gynecol Scand, 90, 737-45.   DOI
23 Kozakowski N, Soleiman A, Pammer J (2008). BMI-1 expression is inversely correlated with the grading of renal clear cell carcinoma. Pathol Oncol Res, 14, 9-13.   DOI
24 Li DW, Tang HM, Fan JW, et al (2010). Expression level of Bmi-1 oncoprotein is associated with progression and prognosis in colon cancer. J Cancer Res Clin Oncol, 136, 997-1006.   DOI
25 Zheng HC, Li XH, Hara T, et al (2008). Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch, 452, 525-34.   DOI
26 Zheng HC, Xu XY, Yu M, et al (2010). The role of Reg IV gene and its encoding product in gastric carcinogenesis. Hum Pathol, 41, 59-69.   DOI
27 Li W, Li Y, Tan Y, Ma K, Cui J (2010). Bmi-1 is critical for the proliferation and invasiveness of gastric carcinoma cells. J Gastroenterol Hepatol, 25, 568-75.   DOI
28 Liu WL, Guo XZ, Zhang LJ, et al (2010). Prognostic relevance of Bmi-1 expression and autoantibodies in esophageal squamous cell carcinoma. BMC Cancer, 10, 467.   DOI
29 Milyavsky M, Shats I, Erez N, et al (2009). Prolonged culture of telomerase-immortalized human fibroblasts leads to a premalignant phenotype. Cancer Res, 63, 7147-57.
30 Qin ZK, Yang JA, Ye YL, et al (2010). Expression of Bmi-1 is a prognostic marker in bladder cancer. BMC Cancer, 9, 61.
31 Song LB, Li J, Liao WT, et al (2009). The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest, 119, 3626-36.   DOI