Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study

Vrzalikova, Katerina; Skarda, J; Ehrmann, Jiří; Murray, Paul G.; Fridman, Eduard; Kopolovic, J.; Knizetova, Petra; Hajdúch, Marián; Klein, Jiří; Kolek, Vı́tězslav; Radová, Lenka; Kolář, Zdeněk

doi:10.1007/s00432-008-0361-y

Cited by 89 publications

(79 citation statements)

References 38 publications

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“…11,12 In previous NSCLC studies, Vonlanthen et al 18 reported no association of Bmi1 expression with tumor characteristics (proliferation rate, differentiation, and size) or prognosis, whereas Vrzalikova et al 20 reported that Bmi1 expression was correlated with advanced stage and poor disease-free survival, but not with overall survival. For other types of cancer, some studies demonstrated that overexpression of Bmi1 was correlated with a poor prognosis [42][43][44] ; however, others reported that loss of Bmi1 expression was correlated with an aggressive phenotype, indicating a protective role of the Bmi1 protein.…”

Section: Bmi1 and Ezh2 Expression In Nsclc/kikuchi Et Almentioning

confidence: 99%

“…16,17 In previous studies on NSCLC, normal bronchial epithelial cells had abundant Bmi1 expression, whereas tumor cells had various expression patterns. 18,19 Vrzalikova et al reported that high Bmi1 expression was correlated with advanced stage and with poor disease-free survival in patients with early stage NSCLC who had received adjuvant chemotherapy, 20 whereas another group reported no association between Bmi1 expression and tumor characteristics (proliferation rate, differentiation, size, histology) or prognosis. 18 Thus, the clinical and clinicopathologic value of Bmi1 in NSCLC remains controversial.…”

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confidence: 99%

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Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance

Kikuchi

Kinoshita

Shimizu

et al. 2010

Cancer

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BACKGROUND:The polycomb group genes Bmi1 polycomb ring finger oncogene (Bmi1) and enhancer of zeste homolog 2 (EZH2) function as transcriptional repressors involved in gene silencing and in the malignant transformation and biologic aggressiveness of several human carcinomas. In the current study, the authors evaluated Bmi1 and EZH2 protein expression in specimens of human nonsmall cell lung cancer (NSCLC). METHODS: The authors conducted an immunohistochemical assessment of 157 surgically resected NSCLCs to evaluate the correlation between Bmi1 and EZH2 expression and various features, including clinical, clinicopathologic, and biologic characteristics. RESULTS: Normal bronchial epithelia revealed abundant expression of Bmi1 and sporadic expression of EZH2. Patients who had high EZH2 expression in tumor cells had a poorer prognosis than patients who had low EZH2 expression in tumor cells all pathologic stages of NSCLC (P ¼.001) and in pathologic stage I NSCLC (P ¼.006). Multivariate analysis revealed that high EZH2 expression was a independent, unfavorable prognostic factor in patients with pathologic stage I disease (P ¼.048). High EZH2 expression was correlated significantly with nonadenocarcinoma histology (P ¼.001), moderate and poor differentiation (P ¼.001), advanced pathologic tumor classification (P ¼.02), and high Ki-67 and cyclin E labeling indices (P < .001). Bmi1 expression, in contrast, was not a significant prognostic factor and was not correlated with any clinicopathologic factors other than early pathologic tumor classification. CONCLU-SIONS: Bmi1 and EZH2 had characteristic and distinctive expression in NSCLCs. High EZH2 expression was correlated with tumor aggressiveness and may provide a novel prognostic marker for NSCLCs. Cancer 2010;116:3015-24.

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Section: Bmi1 and Ezh2 Expression In Nsclc/kikuchi Et Almentioning

confidence: 99%

mentioning

confidence: 99%

Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance

Kikuchi

Kinoshita

Shimizu

et al. 2010

Cancer

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“…7 Katerina et al indicated that Bmi-1 was significantly associated with progression of NSCLC from a tissue microarray study. 8 Hu et al showed that the combination of USP22, PTEN, Bmi-1 and p-AKT markers was the independent prognostic indicator of overall survival in non-small-cell lung cancer. 9 The findings display that Bmi-1 is a significant prognostic factor of poor overall survival in lung adenocarcinoma patients.…”

Section: Introductionmentioning

confidence: 99%

Bmi-1 expression modulates non-small cell lung cancer progression

Xiong

et al. 2015

Cancer Biology & Therapy

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y These authors equally contributed to this work.Keywords: Bmi-1, EMT, invasion, metastasis, NSCLC, progression Abbreviations: NSCLC, non-small cell lung cancer; EMT, epithelial-mesenchymal transition; Bmi-1, B lymphoma Mo-MLV insertion region 1 homolog; IHC, immunohistochemistry; FBS, fetal calf serum; qRT-PCR, quantitative real-time PCR.Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression.

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“…2). In particular, Bmi1 overexpression is correlated with poor prognosis for lung cancer patients (3). Bmi1 is an epigenetic chromatin modifier that acts as a key component of the PRC1 complex to mediate transcriptional repression.…”

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Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion

Dovey

Zacharek

Kim

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

161

165

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Understanding the pathways that control epithelial carcinogenesis is vital to the development of effective treatments. The Polycomb group family member Bmi1 is overexpressed in numerous epithelial tumors, but its role in their development has not been established. We now show a key role for Bmi1 in lung adenocarcinoma. Whereas lung development occurs normally in Bmi1-deficient mice, loss of Bmi1 decreases the number and progression of lung tumors at a very early point in an oncogenic K-ras-initiated mouse model of lung cancer. This correlates with a defect in the ability of Bmi1-deficient putative bronchiolalveolar stem cells (BASCs) to proliferate in response to the oncogenic stimulus. Notably, in the absence of oncogenic K-ras, Bmi1-deficient BASCs show impaired proliferation and self-renewal capacity in culture and after lung injury in vivo. Abrogated lung cancer development and BASC self-renewal occur partially in a p19 ARF -dependent manner. Our data suggest that Bmi1 deficiency suppresses tumor development by limiting the expansion potential of BASCs, the apparent lung cancer cells of origin. Because Bmi1 is elevated in additional tumor types, this suggests that Bmi1 plays a key role in regulating proliferation of both stem cells and tumor cells in diverse adult epithelial tissues.Arf ͉ Ink4a ͉ non-small-cell lung cancer ͉ p16

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Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study

Abstract: Our results suggest that Bmi-1 is significantly associated with progression of NSCLC and might serve as a prognostic marker of adverse disease outcome.

Cited by 89 publications

References 38 publications

Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance

Distinctive expression of the polycomb group proteins Bmi1 polycomb ring finger oncogene and enhancer of zeste homolog 2 in nonsmall cell lung cancers and their clinical and clinicopathologic significance

Bmi-1 expression modulates non-small cell lung cancer progression

Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion

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