TLR3 serves as a novel diagnostic and prognostic biomarker and is closely correlated with immune microenvironment in three types of cancer

Abstract

Background: Toll-like receptor 3 (TLR3) plays an important role in both innate and adaptive immunity, but the prognostic value of TLR3 in heterogeneous tumors and the correlations between TLR3 expression and immune infiltration of heterogeneous tumors remain unclear.Methods: We investigated the expression of TLR3 in a variety of tumors and focused on the diagnostic and prognostic values of TLR3 in kidney renal clear cell carcinoma (KIRC), pancreatic adenocarcinoma (PAAD) and brain lower grade glioma (LGG) by GEPIA, DriverDBv3, UALCAN, TIMER, LinkedOmics, STRING, GeneMANIA and FunRich, as well as the possible mechanisms of TLR3 affecting tumor prognosis were discussed. Additionally, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to validate TLR3 expression in early KIRC. We also compared the expression of TLR3 in the plasma of early KIRC patients and normal controls by enzyme linked immunosorbent assay (ELISA).Results: TLR3 expression was significantly different in multiple tumors compared with paracancerous nontumor tissues. Elevated expression of TLR3 contributed to the prolonged survival outcome in KIRC patients. Suppressed expression of TLR3 contributed to the prolonged survival outcome in LGG and PAAD patients. Moreover, TLR3 was significantly elevated in stage1, grade1 and N0 of KIRC. The expression and function of TLR3 in KIRC, LGG and PAAD were closely related to tumor immune microenvironment. TRAF6 was a key gene in the interactions between TLR3 and its interacting genes. Finally, the results of RT-qPCR and ELISA indicated that TLR3 expression levels were significantly raised in renal tissue and plasma of early KIRC patients.Conclusion: TLR3 has the potential to be a diagnostic biomarker of KIRC, LGG and PAAD as well as a biomarker for evaluating the prognosis of KIRC, LGG and PAAD, particularly for the early diagnosis of KIRC. TLR3 affects tumors mainly by acting on the immune microenvironment of KIRC, LGG and PAAD. These findings could lead to new insights into the immunotherapeutic targets for KIRC, LGG, and PAAD.

Anoikis-related gene signature associates with the immune infiltration and predicts the prognosis of glioma patients

“…TLR3 (Toll-like receptor 3) is a member of the TLR family, which mediates the transcription induction of type I interferon, pro-in ammatory cytokines and chemokines 42 , and its primary function is in the activation of the innate immune system in the process of anti-virus 43,44 . A recent bioinformatic study indicated that TLR3 can be a prognosis biomarker for many types of cancers 45 . In human non-small-cell lung cancer, TLR3 activation induces apoptosis 46 .…”

Focus on Therapeutic Options for Surgically Resectable Pancreatic Adenocarcinoma Based on Novel Biomarkers

“…These investigations have aimed to explore their associations with tumorigenesis, cancer progression, the modulation of tumor immune cell infiltration, the expression of immune checkpoints, and the upregulation of immunosuppressive genes. These molecules hold potential as future biomarkers for diagnosing and prognosing pancreatic adenocarcinoma, as well as serving as therapeutic targets for tumor immunotherapy [39][40][41][42][43][44].…”

RHCG-Upregulating Polymeric Nanoparticles for Sensitized Chemotherapy and Immunotherapy in Head and Neck Squamous Cell Carcinoma

“…The toll-like receptors (TLRs) are critical in innate immunity as pattern recognition receptors. − TLR3 is predominantly expressed in innate immune cells, such as dendritic cells (Figure S1), macrophages, and natural killer cells, which have been exploited extensively to enhance an antitumor immune response. − Notably, TLR3 is highly expressed in many types of human solid tumors, including lung and breast cancer, oral cell squamous carcinoma, cervical carcinoma, and head and neck carcinoma. , This receptor is located in intracellular cytoplasm or endosomes and sensed double-stranded RNA (dsRNA) viruses, including polyriboinosinic:polyribocytidylic acid (poly (I:C)). − TLR3 signaling activates NF-κB and upregulates the RHCG gene.…”

“…30−32 Notably, TLR3 is highly expressed in many types of human solid tumors, including lung and breast cancer, oral cell squamous carcinoma, cervical carcinoma, and head and neck carcinoma. 33,34 This receptor is located in intracellular cytoplasm or endosomes and sensed double-stranded RNA (dsRNA) viruses, including polyriboinosinic:polyribocytidylic acid (poly (I:C)). 35−37 TLR3 signaling activates NF-κB and upregulates the RHCG gene.…”