TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment

Abstract

Background. Clear cell renal cancer (KIRC) is one of the most common cancers globally, with a poor prognosis. TLRs play a vital role in anticancer immunity and the regulation of the biological progress of tumour cells. However, the precise role of TLRs in KIRC is still ambiguous. Methods. Various bioinformatics analysis and clinical validation of tissues were performed to evaluate the prognostic value of TLRs and their correlation with immune infiltration in KIRC. Results. The expression of TLR2/3/7/8 was increased at both mRNA and protein levels in KIRC. TLRs in KIRC were involved in the activation of apoptosis, EMT, RAS/MAPK, and RTK pathways, as well as the inhibition of the cell cycle and the hormone AR pathway. Drug sensitivity analysis revealed that high expression of TLR3 and low expression of TLR7/9/10 were resistant to most of the small molecules or drugs from CTRP. Enrichment analyses showed that TLRs were mainly involved in innate immune response, toll-like receptor signalling pathway, NF-kappa B signalling pathway, and TNF signalling pathway. Furthermore, a high-level TLR3 expression was associated with a favourable prognosis in KIRC. Validation research further confirmed that TLR3 expression was increased in KIRC tissues, and high TLR3 levels were associated with poor overall survival. Moreover, TLR3 in KIRC showed a positive association with an abundance of immune cells, including B-cells, CD4+ T-cells, CD8+ T-cells, macrophage, neutrophils, and dendritic cells, and the expression of the immune biomarker sets. Several TLR3-associated kinase, miRNA, or transcription factor targets were also identified in KIRC. Conclusion. Our results indicate that TLR3 serves as a prognostic biomarker and associated with immune infiltration in KIRC. This work lays a foundation for further studies on the role of TLR3 in the carcinogenesis and progression of KIRC.

PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma

“…al, 2020) [40]. Increased immune cell infiltration levels are linked to heightened tumor aggressiveness in a range of cancers including breast cancer, kidney renal clear cell carcinoma, uveal melanoma, pancreatic cancer, and osteosarcoma [41][42][43][44][45][46][47][48]. In gliomas, including LGG, increased immune cell infiltration levels showed poor prognosis and more aggressive phenotypes [21,22,[49][50][51][52][53][54][55][56][57].…”

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

“…A number of studies showed that the five genes described above were associated with the prognosis, progression, development, and treatment response of a wide variety of tumors, including small cell lung cancer [40], lower-grade gliomas [41], PCa [42,43], prostate cancer [44], clear cell renal cell carcinoma [45,46], and stomach adenocarcinoma [47]. For instance, TLR3 expression was positively correlated with survival time in stomach adenocarcinoma [47].…”

“…ese results suggest that the mutations of the five genes may be a prognostic signature of PCa. ere is plenty of evidence showing the associations of the PLCG1, TLR3, and CXCL9 genes with immune infiltration in tumor microenvironment [42,45,47,58,59]. ese genes were associated with the prognosis of tumors by regulating the abundance of tumor-infiltrating dendritic cells, macrophages, neutrophils, natural killer (NK) cells, B cells, and T cells [42,45,47,59,60].…”

“…ere is plenty of evidence showing the associations of the PLCG1, TLR3, and CXCL9 genes with immune infiltration in tumor microenvironment [42,45,47,58,59]. ese genes were associated with the prognosis of tumors by regulating the abundance of tumor-infiltrating dendritic cells, macrophages, neutrophils, natural killer (NK) cells, B cells, and T cells [42,45,47,59,60]. TLR3 has been identified to be associated with the infiltration of immune cells, including dendritic cells, macrophages, neutrophils, NK cells, B cells, and T cells, in the renal clear cell carcinoma [45].…”

“…ese genes were associated with the prognosis of tumors by regulating the abundance of tumor-infiltrating dendritic cells, macrophages, neutrophils, natural killer (NK) cells, B cells, and T cells [42,45,47,59,60]. TLR3 has been identified to be associated with the infiltration of immune cells, including dendritic cells, macrophages, neutrophils, NK cells, B cells, and T cells, in the renal clear cell carcinoma [45]. Also, the TLR3 expression level in stomach adenocarcinoma was correlated with the abundance of immune cells [47].…”