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Updated: Jun 29, 2025
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Published on: February 8, 2018
Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma
Yaguang Hu1, Yanan Gu2, Yichen Song3
1Department of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yan-ta West Road, Xi'an, Shaanxi, 710061, China.
Abstract:
Human Toll-like receptor (TLR) family plays a crucial role in immunity and cancer progression. However, the specific role of human Toll-like receptor 4 (TLR4) in kidney renal clear cell carcinoma (KIRC) remains obscure. Thus, we used single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies to evaluate the expression and prognostic value of TLR4 in KIRC. In our study, we observed that TLR4 was over expressed in KIRC tissues compared to normal renal tissues. And the expression of TLR4 was higher in macrophages/monocytes than other cell types. Besides, there is a close association between TLR4 expression and immune cell infiltration (Neutrophils, Macrophages, T cells and B cells) in KIRC. Immunohistochemical staining also showed that TLR4 was overexpressed in inflammatory infiltration renal tissue compared with normal tissue. Meanwhile, high expression of TLR4 exhibited correlations with improved survival, lower tumor grade and stage. Interestingly, the protective significance of TLR4 only showed in female patients (HR = 0.37, P < 0.01), other than male patients (HR = 0.71, P = 0.08) with KIRC. Consistently, KIRC samples with lymph node metastasis showed lower expression of TLR4. Knockdown of TLR4 in 786-O cell line increased cell proliferation and clonogenic capacity. In summary, this study found TLR4 could inhibit the progression of kidney cancer and was associated with improved survival in KIRC. The overexpression of TLR4 in macrophages and the close association between TLR4 and immune cell infiltration also underline the critical role of TLR4 in building the immune microenvironment for kidney cancer. These results may offer insights into the mechanism and immune microenvironment of kidney cancer.
Insights
Toll-like receptor 4 (TLR4) inhibits kidney cancer progression and improves survival in female patients. Its overexpression in macrophages and association with immune cell infiltration highlight its role in the kidney cancer immune microenvironment.
Area of Science:
- Immunology
- Oncology
- Renal cell carcinoma research
Background:
- The Toll-like receptor (TLR) family is vital in immunity and cancer.
- The specific function of Toll-like receptor 4 (TLR4) in kidney renal clear cell carcinoma (KIRC) is not well understood.
Purpose of the Study:
- To investigate the expression and prognostic implications of TLR4 in KIRC.
- To explore the association between TLR4 and the tumor immune microenvironment in KIRC.
Main Methods:
- Analysis of single-cell and bulk RNA sequencing data.
- In vitro studies including cell line experiments.
- Immunohistochemical staining of KIRC tissues.
Main Results:
- TLR4 is overexpressed in KIRC tissues and higher in macrophages/monocytes.
- TLR4 expression correlates with increased immune cell infiltration (neutrophils, macrophages, T cells, B cells).
- High TLR4 expression is linked to better survival, lower tumor grade/stage, particularly in females, and reduced lymph node metastasis. TLR4 knockdown increased cell proliferation.
Conclusions:
- TLR4 inhibits KIRC progression and is associated with improved survival.
- TLR4 plays a critical role in shaping the kidney cancer immune microenvironment, especially within macrophages.
- Findings offer insights into KIRC mechanisms and immune interactions.
