Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer

Callagy, Grace; Webber, Mark; Pharoah, Paul D.P.; Caldas, Carlos

doi:10.1186/1471-2407-8-153

Cited by 167 publications

(160 citation statements)

References 55 publications

(133 reference statements)

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“…the association between its expression and patient survival result is quite conflicting and seems tissue-specific. For example: The different results in CLL and breast cancer may be determined by the balance between the dual function of Bcl-2 protein (Callagy et al, 2008). These findings were in parallel with those results in colorectal cancer, breast cancer, non-small-cell lung cancer, renal cancer and head and neck cancer.…”

Section: Discussionmentioning

confidence: 53%

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran

Mirmajidi¹,

Ataee²,

Barzegar³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. Materials and Methods: A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. Results: Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. Conclusions: On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.

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Section: Discussionmentioning

confidence: 53%

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran

Mirmajidi¹,

Ataee²,

Barzegar³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Moreover, the model was significantly associated with both BCSS and metastasis free interval, independently of other factors. This algorithm reiterates the documented prognostic values of these three markers and underscoring the central biologic role played by each of these three markers in breast cancer progression [31][32][33]. According to these results, this small or pruned panel of biomarkers could be used with acceptable success in distant recurrence prediction.…”

Section: Discussionmentioning

confidence: 74%

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

Aleskandarany

Soria

Green

et al. 2015

Breast Cancer Res Treat

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Accurate distant metastasis (DM) prediction is critical for risk stratification and effective treatment decisions in breast cancer (BC). Many prognostic markers/models based on tissue marker studies are continually emerging using conventional statistical approaches analysing complex/dimensional data association with DM/poor prognosis. However, few of them have fulfilled satisfactory evidences for clinical application. This study aimed at building DM risk assessment algorithm for BC patients.A well-characterised series of early invasive primary operable BC (n=1902), with immunohistochemical (IHC) expression of a panel of biomarkers (n=31) formed the material of this study. Decision tree algorithm was computed using WEKA software, utilising quantitative biomarkers' expression and the absence/presence of distant metastases.Fifteen biomarkers were significantly associated with DM, with six temporal subgroups characterised based on time-to-development of DM ranging from < 1 year to > 15 years of follow-up. Of these 15 biomarkers, 10 had a significant expression pattern where Ki67LI, HER2, p53, N-cadherin, P-cadherin, PIK3CA and TOMM34 showed significantly higher expressions with earlier development of DM. In contrast, higher expressions of ER, PR, and BCL2, were associated with delayed occurrence of DM. DM prediction algorithm was built utilising cases informative for the 15 significant markers. Four risk groups of patients were characterised. Three markers; p53, HER2 and BCL2 predicted the probability of DM, based on software-generated cut-offs, with a precision rate of 81.1% for positive predictive value and 77.3%, for the negative predictive value.This algorithm reiterates the reported prognostic values of these three markers and underscores their central biologic role in BC progression. Further independent validation of this pruned panel of biomarkers is therefore warranted.3

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“…3,9,10 Also, clinical observations reporting that BCL2 expression in breast cancer can be associated with a favorable prognosis suggests a possible beneficial role for BCL2 in suppressing tumor progression and metastasis. 11 In our investigation, BCL2 overexpression inhibited cell adhesion, spreading and motility in NIH3T3 and MCF7 cells, which was associated with increased actin polymerization. 12 Taken together, these multiple and complex functions suggest that BCL2 can act as a "cell defender" to protect against signaling, which results in cell migration, division and death.…”

Section: Introductionmentioning

confidence: 96%

BCL2 interaction with actin in vitro may inhibit cell motility by enhancing actin polymerization

Zhang

Akiyama

et al. 2011

Cell Adhesion & Migration

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In addition to its well-defined role as an antagonist in apoptosis, we propose that BCL2 may act as an intracellular suppressor of cell motility and adhesion under certain conditions. Our evidence shows that, when overexpressed in both cancer and non-cancer cells, BCL2 can form a complex with actin and gelsolin that functions to decrease gelsolin-severing activity to increase actin polymerization and, thus, suppress cell adhesive processes. The linkage between increased BCL2 and increased actin polymerization on the one hand and suppression of cell adhesion, spreading and motility on the other hand, is a novel observation that may provide a plausible explanation for why BCL2 overexpression in some tumors is correlated with improved patient survival. In addition, we have identified conditions in vitro in which F-actin polymerization can be increased while cell motility is reduced. These findings underscore the possibility that BCL2 may be involved in modulating cytoskeleton reorganization and may provide an opportunity to explore signal transduction pathways important for cell adhesion and migration and to develop small molecule therapies for suppression of cancer metastasis.

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Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer

Cited by 167 publications

References 55 publications

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran

Markers of progression in early-stage invasive breast cancer: a predictive immunohistochemical panel algorithm for distant recurrence risk stratification

BCL2 interaction with actin in vitro may inhibit cell motility by enhancing actin polymerization

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