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Overexpression of the secretory small GTPase Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis.

Zhang JX, Huang XX, Cai MB, Tong ZT, Chen JW, Qian D, Liao YJ, Deng HX, Liao DZ, Huang MY, Zeng YX, Xie D, Mai SJ - J Transl Med (2012)

Bottom Line: Furthermore, patients with high expression of Rab27B had inferior survival outcomes.Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001).Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651# Dongfeng Road East, Guangzhou 510060, China.

ABSTRACT

Background: The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients.

Methods: The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression.

Results: We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.

Conclusion: Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.

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Related in: MedlinePlus

Correlation between the expression of Rab27B and EMT markers in BC tissues. (A) High expression of Rab27B in BC was accompanied by elevated level of vimentin, fibronectin, and absence of E-cadherin, β-catenin (upper panel). (B) Low expression of Rab27B in BC was accompanied by absence of vimentin, fibronectin, and elevated level of E-cadherin, β-catenin (lower panel).
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Figure 3: Correlation between the expression of Rab27B and EMT markers in BC tissues. (A) High expression of Rab27B in BC was accompanied by elevated level of vimentin, fibronectin, and absence of E-cadherin, β-catenin (upper panel). (B) Low expression of Rab27B in BC was accompanied by absence of vimentin, fibronectin, and elevated level of E-cadherin, β-catenin (lower panel).

Mentions: To explore the relationship of Rab27B and EMT process, IHC staining of was performed in 221 primary BC tissues. Representative IHC staining of EMT markers in BC tissues is shown in Figure 3. We observed that Rab27B expression level was positively correlated with the expression level of mesenchymal markers: Vimentin (rs = 0.289, P <0.001, n = 221, Spearman’s correlation analysis), Fibronectin (rs = 0.327, P < 0.001, n = 221, Spearman’s correlation analysis), and inversely correlated with epithelial markers: E-cadherin (rs = −0.226, P = 0.001, n = 221, Spearman’s correlation analysis), β-catenin (rs = −0.389, P < 0.001, n = 221, Spearman’s correlation analysis).These data illustrated that overexpression of Rab27B contributed to the EMT process in BC progression.


Overexpression of the secretory small GTPase Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis.

Zhang JX, Huang XX, Cai MB, Tong ZT, Chen JW, Qian D, Liao YJ, Deng HX, Liao DZ, Huang MY, Zeng YX, Xie D, Mai SJ - J Transl Med (2012)

Correlation between the expression of Rab27B and EMT markers in BC tissues. (A) High expression of Rab27B in BC was accompanied by elevated level of vimentin, fibronectin, and absence of E-cadherin, β-catenin (upper panel). (B) Low expression of Rab27B in BC was accompanied by absence of vimentin, fibronectin, and elevated level of E-cadherin, β-catenin (lower panel).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539959&req=5

Figure 3: Correlation between the expression of Rab27B and EMT markers in BC tissues. (A) High expression of Rab27B in BC was accompanied by elevated level of vimentin, fibronectin, and absence of E-cadherin, β-catenin (upper panel). (B) Low expression of Rab27B in BC was accompanied by absence of vimentin, fibronectin, and elevated level of E-cadherin, β-catenin (lower panel).
Mentions: To explore the relationship of Rab27B and EMT process, IHC staining of was performed in 221 primary BC tissues. Representative IHC staining of EMT markers in BC tissues is shown in Figure 3. We observed that Rab27B expression level was positively correlated with the expression level of mesenchymal markers: Vimentin (rs = 0.289, P <0.001, n = 221, Spearman’s correlation analysis), Fibronectin (rs = 0.327, P < 0.001, n = 221, Spearman’s correlation analysis), and inversely correlated with epithelial markers: E-cadherin (rs = −0.226, P = 0.001, n = 221, Spearman’s correlation analysis), β-catenin (rs = −0.389, P < 0.001, n = 221, Spearman’s correlation analysis).These data illustrated that overexpression of Rab27B contributed to the EMT process in BC progression.

Bottom Line: Furthermore, patients with high expression of Rab27B had inferior survival outcomes.Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001).Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651# Dongfeng Road East, Guangzhou 510060, China.

ABSTRACT

Background: The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC) in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients.

Methods: The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC) assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT). Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA), 30 ductual carcinoma in situ (DCIS) and 40 metastatic lymph nodes (LNs). The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to Rab27B expression.

Results: We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P < 0.001). The elevated expression of Rab27B was closely correlated with lymph node metastasis, advanced clinical stage, ascending pathology classification, and positive ER status. Furthermore, patients with high expression of Rab27B had inferior survival outcomes. Multivariate Cox regression analysis proved that Rab27B was a significantly independent risk factor for patients' survival (P < 0.001). Furthermore, a significant positive relationship was observed between Rab27B expression and elevated mesenchymal EMT markers.

Conclusion: Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.

Show MeSH
Related in: MedlinePlus