Prognostic Value of Myeloid Differentiation Primary Response 88 and Toll-Like Receptor 4 in Breast Cancer Patients

Abstract

PurposeBreast 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).MethodsWe 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.ResultsIn 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).ConclusionsTLR4-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.

The role of toll-like receptor 4 in tumor microenvironment

“…The expression of MTDH are presented at a higher levels in TLR4 positive breast cancer cells (MDA-MB-231,MCF-7,and MDA-MB-468) than that in TLR4 negative T47D cell lines after treated with LPS, suggesting the pro-tumor role of TLR4 expressed on tumor cells [ 92 ]. Furthermore, TLR4 has also been reported correlation with metastasis of breast cancer cells [ 93 , 94 ] and has down favor on poor survival of breast cancer patients [ 95 ].…”

Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker

“…Worldwide, breast cancer remains a major cause of female deaths ( 9 ). Breast cancer can be broadly classified into four major molecular subtypes, depending on the specific genetic profile (i.e., luminal A, luminal B, triple-negative/basal-like and HER2 status) ( 10 , 11 ).…”

Toll-like receptor stimulation in cancer: A pro- and anti-tumor double-edged sword

“…In a model of diethylnitrosamine-induced HCC in wild-type and TLR4-deficient mice, TLR4 stimulation of resident liver cells by intestinal microbiota was required for promoting HCC (Dapito et al, 2012). Finally, several studies demonstrated TLR4 overexpression by tumor cells associated with poor clinical outcome in breast cancer Ma et al, 2014), colorectal cancer (Cammarota et al, 2010) and pancreatic ductal adenocarcinoma (Zhang et al, 2010).…”