Expression level of Bmi-1 oncoprotein is associated with progression and prognosis in colon cancer

Li, Dawei; Tang, Huamei; Fan, Junwei; Yan, Dongwang; Zhou, Chongzhi; Li, Shuxia; Wang, Xiaoliang; Peng, Zhihai

doi:10.1007/s00432-009-0745-7

Cited by 104 publications

(96 citation statements)

References 27 publications

(23 reference statements)

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“…Bmi1 mRNA and protein overexpression were previously demonstrated in CRC tumor (5,7) and were positively correlated with tumor stage, invasion and metastasis (6), as well as with poor disease-free and overall survival (6,19), suggesting that Bmi1 is a promising prognostic biomarker in CRC patients. To the best of our knowledge, this study was the first to further demonstrate that the changes in plasma Bmi1 mRNA level prior to and following resection of the primary tumor was prognostic for the development of metastasis, indicating the potential of circulating Bmi1 mRNA levels as a non-invasive, convenient and relatively cost-effective surrogate biomarker for the management of postoperative CRC patients and possibly patients with other types of cancer in which Bmi1 is also overexpressed.…”

Section: Discussionmentioning

confidence: 71%

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

Pun¹,

Chan²,

Chun³

et al. 2014

Molecular and Clinical Oncology

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Abstract. Bmi1 is overexpressed in gastrointestinal cancers, including colorectal cancer (CRC); however, its role as a non-invasive biomarker in CRC has not been established. The aim of this study was to compare the plasma Bmi1 mRNA levels prior to and following curative resection of the primary tumor in CRC patients and to determine their association with the clinicopathological parameters. The plasma Bmi1 mRNA level was measured by quantitative polymerase chain reaction and expressed as cycle threshold value. There was no significant difference between the overall pre-and postoperative plasma Bmi1 mRNA level (31.73±2.63 vs. 31.93±2.88, respectively; P=0.614) in 45 CRC patients. However, when grouped into non-metastatic and metastatic CRC patients, the postoperative Bmi1 transcript level was found to be significantly lower compared to the preoperative level in patients with non-metastatic CRC (32.13±2.677 31.44±2.764, respectively; P=0.041), whereas there was a trend towards a higher postoperative Bmi1 transcript level compared to the preoperative level in the metastatic counterpart (30.85±3.916 vs. 33.27±0.718, respectively; P=0.164). Furthermore, when the patients were categorized into two groups according to their plasma Bmi1 postoperative vs. preoperative level status, we observed that patients without a reduction in the postoperative plasma Bmi1 mRNA levels exhibited a significantly higher rate of distant metastasis following primary resection (P=0.017) and a significantly worse prognosis regarding disease-free survival (P=0.016) when compared to the reduced postoperative plasma Bmi1 level counterparts. In conclusion, plasma Bmi1 mRNA levels may serve as a non-invasive biomarker for monitoring occult metastasis and predicting the development of distant metastasis. IntroductionColorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, with >1.2 million new cancer cases and 608,700 deaths estimated to have occurred in 2008 (1). Recent advances in therapeutic strategies and surgical techniques have significantly improved the prognosis of CRC patients with primary disease; however, metastasis is a major concern for CRC patients and physicians. Thirty-five percent of CRC patients have metastatic tumors at the time of diagnosis and 33-50% of the patients without metastases will progress to stage IV during the course of their disease (1,2). Hence, it is necessary to develop prominent biomarkers for detecting the presence of occult metastasis, as well as for predicting the development of future metastasis, which may provide a useful reference for the therapeutic management of CRC patients.Potential stem cell marker, Bmi1, is a member of the polycomb-repressive complex 1, with a key role in gene silencing through chromatin modifications (3,4). In addition to the proposed role for Bmi1 as a key regulator of cell growth control/senescence mechanisms, accumulating evidence supports the role of Bmi1 in tumorigenesis. Bmi1 is overexpressed in a variety of human cancers and it...

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Section: Discussionmentioning

confidence: 71%

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

Pun¹,

Chan²,

Chun³

et al. 2014

Molecular and Clinical Oncology

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“…On the day of measuring the growth rate of untreated and transfected cells (24,48,72 and 96 h, respectively), 100 μl of spent medium was replaced with an equal volume of fresh medium containing 10% CCK-8, then cells were continued to incubate at 37˚C for 3 h, and the absorbance was finally determined at 450 nm using Microplate reader.…”

Section: Methodsmentioning

confidence: 99%

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

Liu²,

Lv³

et al. 2011

Oncol Rep

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Abstract.It is well documented that B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), widely overexpressed in the vast majority of malignancies, plays an essential role in the occurrence and development of several different tumors. Here, we report Bmi-1 siRNA-mediated cell proliferation inhibition and cell apoptosis in vitro and in vivo in the human breast carcinoma cell line MCF-7. Our results demonstrated that Bmi-1 siRNA effectively down-regulated the expression of Bmi-1, inhibited cell proliferation in vitro and in vivo, evoked cell cycle arrest in the G 0 /G 1 phase and induced cell apoptosis in MCF-7 cells, coupled with decrease in cyclin D1, cyclin E, cdk2, bcl-2 and Ki-67 expression and Akt phosphorylation levels and an increase of p21 and bax expression and activities of caspase-3/-9. Taken together, our results suggest that Bmi-1 may be a potential molecular target for the therapy of breast carcinoma.

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“…The p53 pathway is usually inactivated by TP53 mutation, amplification of MDM2 or p14ARF deletion in a number of human cancers (37,38). Previous studies have demonstrated that Bmi-1 is a potent repressor of the p14ARF-MDM2-p53 pathway (13,39,40). Inactivation of the p53 pathway by Bmi-1 has been identified in lymphomagenesis and oncogenesis in human non-small cell lung cancer (15,37,41).…”

Section: Decreased Expression Normal Expression Overexpression ------mentioning

confidence: 99%

“…As a transcriptional repressor through chromatin modification, Bmi-1 is involved in axial patterning, cell cycle regulation, hematopoiesis and senescence (7,8). Overexpression of Bmi-1 has been observed in a variety of human cancers, including gastric (9), breast (10), colorectal (11) and head and neck cancers (12), and it was also observed that expression of Bmi-1 is associated with the development of tumors (13,14). It was reported that overexpression of Bmi-1 in primary human cancer cells may cause downregulation of the INK4a-ARF locus and affect the pathway of p14ARF-Mdm2-p53 (15).…”

Section: Introductionmentioning

confidence: 99%

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B-cell specific Moloney leukemia virus insert site 1 and peptidyl arginine deiminase IV positively regulate carcinogenesis and progression of esophageal squamous cell carcinoma

Wang¹,

Ji²,

Sun³

et al. 2017

Oncology Letters

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Abstract. High expression of B-cell specific Moloney leukemia virus insert site 1 (Bmi-1) and peptidyl arginine deiminase IV (PADI4) is associated with esophageal carcinoma. However, few studies have investigated the association between the Bmi-1 and PADI4 genes. The aim of the present study was to evaluate the expression of Bmi-1 and PADI4 and identify the association between the Bmi-1 and PADI4 genes in esophageal squamous cell carcinoma (ESCC) tissues. Bmi-1 and PADI4 gene expression levels were measured using immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction in ESCC tissues from 86 patients who had not received pre-operative chemoradiation. The results revealed that the Bmi-1 and PADI4 genes had increased expression in carcinoma tissues compared with pericarcinous tissue (P<0.05). Bmi-1 gene expression was revealed to be associated with differentiation degree, clinical stage and lymph node metastasis (P<0.05), but had no association with gender, age or depth of invasion (P>0.05). The expression of PADI4 was associated with clinical stage, depth of invasion and lymph node metastasis (P<0.05), but was not associated with gender, age or differentiation degree (P>0.05). In addition, there was a positive association between Bmi-1 and PADI4 gene expression in ESCC (P<0.05). These results indicated that Bmi-1 and PADI4 positively regulate carcinogenesis and progression of ESCC.

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Expression level of Bmi-1 oncoprotein is associated with progression and prognosis in colon cancer

Abstract: We have shown that expression of Bmi-1 was elevated in colon cancer and might serve as an independent prognostic marker.

Cited by 104 publications

References 27 publications

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients

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

B-cell specific Moloney leukemia virus insert site 1 and peptidyl arginine deiminase IV positively regulate carcinogenesis and progression of esophageal squamous cell carcinoma

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