Limits...
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.

Show MeSH

Related in: MedlinePlus

The expression pattern of Rab27B in BC tissues. (A) Western blot analysis of Rab27B protein expression in 8 representative paired BCs (T) and NATs (N). Equal loading of protein is shown by α-tubulin. (B) Rab27B mRNA and protein expression in human BCs (T) and NATs (N) by Real-time PCR (left panel) and IHC analysis (right panel). Rab27B mRNA and protein expression in 12 primary BCs is upregulated compared to their NATs. (C) Negative staining of Rab27B in normal breast tissue. (D) Weak staining of Rab27B in FA. (E) Moderate staining of Rab27B in DCIS. (F) BC cells showing strong staining of Rab27B. (G) Strong Rab27B staining in metastatic lymph nodes. (H) Statistical analysis revealed a significantly ascending pattern of Rab27B expression ranging from NAT to BC to distant metastases nodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3539959&req=5

Figure 1: The expression pattern of Rab27B in BC tissues. (A) Western blot analysis of Rab27B protein expression in 8 representative paired BCs (T) and NATs (N). Equal loading of protein is shown by α-tubulin. (B) Rab27B mRNA and protein expression in human BCs (T) and NATs (N) by Real-time PCR (left panel) and IHC analysis (right panel). Rab27B mRNA and protein expression in 12 primary BCs is upregulated compared to their NATs. (C) Negative staining of Rab27B in normal breast tissue. (D) Weak staining of Rab27B in FA. (E) Moderate staining of Rab27B in DCIS. (F) BC cells showing strong staining of Rab27B. (G) Strong Rab27B staining in metastatic lymph nodes. (H) Statistical analysis revealed a significantly ascending pattern of Rab27B expression ranging from NAT to BC to distant metastases nodes.

Mentions: To investigate the status of Rab27B gene expression in BC, we used Real-time PCR to measure the mRNA expression in 12 pairs of primary BC and NAT specimens. Compared with their NATs, 8 of 12 BC had upregulated expression. Consistently, western blot and IHC analysis showed that the 8 cases also had higher Rab27B protein expression than adjacent tissues. The BC cases with upregulated expression of Rab27B are shown in Figure 1A and 1B. Interestingly, our IHC and Real-time PCR result in these 12 paired BC and NAT specimens demonstrated the protein and mRNA level of Rab27B are positively correlated (rs = 0.705, P < 0.001). IHC analysis showed that positive expression of Rab27B was primarily observed in the cell cytoplasm and membrane. Immunoreactivity of Rab27B protein in BC ranged from 0 to 7. In normal breast tissues and FA tissues, no or weak Rab27B staining was detected (Figure 1C-D). However, Rab27B showed more positive staining in DCIS tissues, BC tissues and metastatic LNs (Figure 1E-1G). An interesting phenomenon was that Rab27B expression appeared to increase incrementally with the magnitude of cancer progression in tissue ( P < 0.05. Figure 1H).


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)

The expression pattern of Rab27B in BC tissues. (A) Western blot analysis of Rab27B protein expression in 8 representative paired BCs (T) and NATs (N). Equal loading of protein is shown by α-tubulin. (B) Rab27B mRNA and protein expression in human BCs (T) and NATs (N) by Real-time PCR (left panel) and IHC analysis (right panel). Rab27B mRNA and protein expression in 12 primary BCs is upregulated compared to their NATs. (C) Negative staining of Rab27B in normal breast tissue. (D) Weak staining of Rab27B in FA. (E) Moderate staining of Rab27B in DCIS. (F) BC cells showing strong staining of Rab27B. (G) Strong Rab27B staining in metastatic lymph nodes. (H) Statistical analysis revealed a significantly ascending pattern of Rab27B expression ranging from NAT to BC to distant metastases nodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The expression pattern of Rab27B in BC tissues. (A) Western blot analysis of Rab27B protein expression in 8 representative paired BCs (T) and NATs (N). Equal loading of protein is shown by α-tubulin. (B) Rab27B mRNA and protein expression in human BCs (T) and NATs (N) by Real-time PCR (left panel) and IHC analysis (right panel). Rab27B mRNA and protein expression in 12 primary BCs is upregulated compared to their NATs. (C) Negative staining of Rab27B in normal breast tissue. (D) Weak staining of Rab27B in FA. (E) Moderate staining of Rab27B in DCIS. (F) BC cells showing strong staining of Rab27B. (G) Strong Rab27B staining in metastatic lymph nodes. (H) Statistical analysis revealed a significantly ascending pattern of Rab27B expression ranging from NAT to BC to distant metastases nodes.
Mentions: To investigate the status of Rab27B gene expression in BC, we used Real-time PCR to measure the mRNA expression in 12 pairs of primary BC and NAT specimens. Compared with their NATs, 8 of 12 BC had upregulated expression. Consistently, western blot and IHC analysis showed that the 8 cases also had higher Rab27B protein expression than adjacent tissues. The BC cases with upregulated expression of Rab27B are shown in Figure 1A and 1B. Interestingly, our IHC and Real-time PCR result in these 12 paired BC and NAT specimens demonstrated the protein and mRNA level of Rab27B are positively correlated (rs = 0.705, P < 0.001). IHC analysis showed that positive expression of Rab27B was primarily observed in the cell cytoplasm and membrane. Immunoreactivity of Rab27B protein in BC ranged from 0 to 7. In normal breast tissues and FA tissues, no or weak Rab27B staining was detected (Figure 1C-D). However, Rab27B showed more positive staining in DCIS tissues, BC tissues and metastatic LNs (Figure 1E-1G). An interesting phenomenon was that Rab27B expression appeared to increase incrementally with the magnitude of cancer progression in tissue ( P < 0.05. Figure 1H).

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