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Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients.

Ma FJ, Liu ZB, Hu X, Ling H, Li S, Wu J, Shao ZM - PLoS ONE (2014)

Bottom Line: Overall survival (OS) and disease-free survival (DFS) were compared.A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001).In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p = 0.006).

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, P.R. China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China; Department of Breast Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, P.R. China.

ABSTRACT

Purpose: Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).

Methods: We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.

Results: In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p = 0.006).

Conclusions: TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.

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Representative MyD88 immunohistochemical staining in large (200× and 400× magnification) and small images (100× magnification).(A) Low immunostaining of MyD88 in invasive ductal breast carcinoma. (B) High immunostaining of MyD88 in invasive ductal breast carcinoma.
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pone-0111639-g002: Representative MyD88 immunohistochemical staining in large (200× and 400× magnification) and small images (100× magnification).(A) Low immunostaining of MyD88 in invasive ductal breast carcinoma. (B) High immunostaining of MyD88 in invasive ductal breast carcinoma.

Mentions: We then investigated the relationship between the expression levels of MyD88 and TLR4 in clinical breast cancer samples by immunohistochemical staining. Representative images of MyD88 and TLR4 are presented in Figure 2 and Figure 3, respectively. MyD88 staining was primarily observed in the cytoplasm and nuclei of tumor cells. High levels of MyD88 expression were detected in 89 of the 205 cases, whereas low expression levels were found in 116 cases. TLR4 was observed in the cytoplasm and cell membrane by immunostaining. High levels of TLR4 staining were observed in 94 of the 205 breast cancer patients, and low levels of staining were observed in the other 111 cases. A significant positive correlation was observed between the expression of MyD88 and TLR4 (p<0.001, Table 2).


Prognostic value of myeloid differentiation primary response 88 and Toll-like receptor 4 in breast cancer patients.

Ma FJ, Liu ZB, Hu X, Ling H, Li S, Wu J, Shao ZM - PLoS ONE (2014)

Representative MyD88 immunohistochemical staining in large (200× and 400× magnification) and small images (100× magnification).(A) Low immunostaining of MyD88 in invasive ductal breast carcinoma. (B) High immunostaining of MyD88 in invasive ductal breast carcinoma.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4216121&req=5

pone-0111639-g002: Representative MyD88 immunohistochemical staining in large (200× and 400× magnification) and small images (100× magnification).(A) Low immunostaining of MyD88 in invasive ductal breast carcinoma. (B) High immunostaining of MyD88 in invasive ductal breast carcinoma.
Mentions: We then investigated the relationship between the expression levels of MyD88 and TLR4 in clinical breast cancer samples by immunohistochemical staining. Representative images of MyD88 and TLR4 are presented in Figure 2 and Figure 3, respectively. MyD88 staining was primarily observed in the cytoplasm and nuclei of tumor cells. High levels of MyD88 expression were detected in 89 of the 205 cases, whereas low expression levels were found in 116 cases. TLR4 was observed in the cytoplasm and cell membrane by immunostaining. High levels of TLR4 staining were observed in 94 of the 205 breast cancer patients, and low levels of staining were observed in the other 111 cases. A significant positive correlation was observed between the expression of MyD88 and TLR4 (p<0.001, Table 2).

Bottom Line: Overall survival (OS) and disease-free survival (DFS) were compared.A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001).In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p = 0.006).

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, P.R. China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China; Department of Breast Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, P.R. China.

ABSTRACT

Purpose: Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).

Methods: We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.

Results: In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663-6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546-13.098; p = 0.006).

Conclusions: TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy.

Show MeSH
Related in: MedlinePlus