Prognostic role of Toll-like receptors in cancer: a meta-analysis

Wang, Qingwen; Zhang, Tingjun; Xiao, Tingting; Pan, Chenghua; Liu, Xing; Zhao, Yulan

doi:10.2147/tcrm.s171341

Cited by 14 publications

(8 citation statements)

References 45 publications

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“…The expression of TLR4 is significantly increased in a variety of cancers (33). High expression of TLR4 in tumor tissues is associated with poor survival in patients with various cancers (34,35). Although previous studies have demonstrated the potential therapeutic implications of inhibiting TLR4 pathway in cancer treatment, few studies have focused on the specific contribution of MD2, which has been known as an essential cofactor in TLR4 signaling for many years.…”

Section: Discussionmentioning

confidence: 99%

MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway

Fang

et al. 2021

J Gastrointest Oncol

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Background: The toll-like receptor (TLR) is an emerging signaling pathway in tumor invasion and metastasis. The activation of TLRs requires specific accessory proteins, such as the small secreted glycoprotein myeloid differentiation protein 2 (MD2), which contributes to ligand responsiveness.However, the role of MD2 in tumorigenesis and metastasis has rarely been reported. This study aimed to investigate the effects and underlying mechanisms of MD2 on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC).Methods: Cell counting kit 8 (CCK8), cell colony formation, wound healing, and transwell assays were conducted to determine cell viability, proliferation, migration, and invasion, respectively. Quantitative realtime PCR (qRT-PCR) was performed to assess the expression of MD2 in HCC cell lines and human normal liver cell lines as well as the silencing efficiency of MD2 blockage. Western blot and qRT-PCR assays were performed to detect the protein and mRNA expression levels of epithelial mesenchymal transformation (EMT) markers and epidermal growth factor receptor (EGFR) signaling molecules.Results: MD2 was highly expressed in HCC tissues and cell lines. High expression of MD2 was associated with poor prognosis of HCC patients. In addition, MD2 silencing slightly inhibited the proliferation of HepG2 and HCCLM3, and significantly suppressed cell migration and invasion. Furthermore, MD2 blockage could distinctly prevent the EMT process by increasing the protein and mRNA levels of E-cadherin and Occludin, and decreasing the levels of Vimentin, N-cadherin, and Snail. Finally, the phosphorylation level of EGFR as well as its downstream molecular Src, Akt, I-κBα, and p65 were downregulated in HCC cells with MD2 silencing.Conclusions: Our findings suggest that high expression of MD2 may affect the EMT, migration, and invasion via modulation of the EGFR pathway in HCC cells.

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Section: Discussionmentioning

confidence: 99%

MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway

Fang

et al. 2021

J Gastrointest Oncol

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“…The prognostic value of various TLRs has been studied in several malignancies. However, according to a recent meta-analysis, not many studies had been published in this field by 2017, with TLR4 emerging as the most widely studied TLR [13]. This meta-analysis concluded that the elevated expressions of TLR4 and TLR7 predicted worse outcomes in several malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence indicating the prognostic value of TLRs in malignancies has proliferated in recent decades. For instance, a recent meta-analysis demonstrated that elevated TLR4 and TLR7 serve as markers of a poorer prognosis in several malignancies [13]. In CRC patients, TLRs have not been widely investigated.…”

Section: Introductionmentioning

confidence: 99%

High Tissue TLR5 Expression Predicts Better Outcomes in Colorectal Cancer Patients

et al. 2021

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Background: Colorectal cancer (CRC), the third most common cancer globally, caused 881,000 cancer deaths in 2018. Toll-like receptors (TLRs), the primary sensors of pathogen-associated molecular patterns and damage-associated molecular patterns, activate innate and adaptive immune systems and participate in the development of an inflammatory tumor microenvironment. We aimed to explore the prognostic value of TLR3, TLR5, TLR7, and TLR9 tissue expressions in CRC patients. Methods: Using immunohistochemistry, we analyzed tissue microarray samples from 825 CRC patients who underwent surgery between 1982 and 2002 at the Department of Surgery, Helsinki University Hospital, Finland. After analyzing a pilot series of 205 tissue samples, we included only TLR5 and TLR7 in the remainder of the patient series. We evaluated the associations between TLR5 and TLR7 tissue expressions, clinicopathologic variables, and survival. Using the Kaplan-Meier method, we generated survival curves, determining significance using the log-rank test. Univariate and multivariate survival analyses relied on the Cox proportional hazards model. Results: The 5-year disease-specific survival was 55.9% among TLR5-negative (95% confidence interval [CI] 50.6–61.2%) and 61.9% (95% CI 56.6–67.2%; p = 0.011, log-rank test) among TLR5-positive patients. In the Cox multivariate survival analysis adjusted for age, sex, stage, location, and grade, positive TLR5 immunoexpression (hazard ratio [HR] 0.74; 95% CI 0.59–0.92; p = 0.007) served as an independent positive prognostic factor. TLR7 immunoexpression exhibited no prognostic value in the survival analysis across the entire cohort (HR 0.97; 95% CI 0.78–1.20; p = 0.754) nor in subgroup analyses. Conclusions: We show for the first time that a high TLR5 tumor tissue expression associates with a better prognosis in CRC patients.

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“…According to modern theory, inflammation is the main agent causing the development and progression of cancer [5]. The causative mechanism of this process is not well understood.…”

Section: Tlrs In Cancersmentioning

confidence: 99%

“…Meta-analysis has shown that TLR4 and TLR7 expression is significantly associated with poor survival in patients with various types of carcinoma [5]. Indeed, a number of dependencies were described between TLRs polymorphism on the one hand, and infectious diseases and cancer on the other [2].…”

Section: Tlrs In Cancersmentioning

confidence: 99%

The role of Toll-like receptors (TLRs) in virus-related cancers: a mini review

Dworzańska

Polz‐Dacewicz

2020

Current Issues in Pharmacy and Medical Sciences

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The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human Epstein-Barr (EBV) and Papillomavirus-(HPV) related cancers. These viruses are able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. The aim of the study is to review current data and summarize knowledge on the TLRs and their role in the development of cancer, especially viral-related cancers (EBV and HPV). Research work shows a correlation between the TLRs polymorphism and the development of oropharyngeal and gastric cancer (GC), especially related to viral infections. Many studies suggest the important role for TLRs in inflammatory, autoimmune disease and human cancers. However, further efforts are necessary to draw a precise conclusion.

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Prognostic role of Toll-like receptors in cancer: a meta-analysis

Cited by 14 publications

References 45 publications

MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway

MD2 blockage prevents the migration and invasion of hepatocellular carcinoma cells via inhibition of the EGFR signaling pathway

High Tissue TLR5 Expression Predicts Better Outcomes in Colorectal Cancer Patients

The role of Toll-like receptors (TLRs) in virus-related cancers: a mini review

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