Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:75

Enthalten in:

Molecular and cellular probes - 75(2024) vom: 07. Apr., Seite 101959

Sprache:

Englisch

Beteiligte Personen:

Hu, Yaguang [VerfasserIn]
Gu, Yanan [VerfasserIn]
Song, Yichen [VerfasserIn]
Zhao, Yuelei [VerfasserIn]
Wang, Jiachen [VerfasserIn]
Ma, Junchi [VerfasserIn]
Sui, Fang [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Pathology
Prognosis
Renal cell carcinoma
Single-cell RNA sequencing
TCGA
Toll-like receptor 4

Anmerkungen:

Date Revised 08.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1016/j.mcp.2024.101959

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM37069323X