Molecular characteristics and therapeutic implications of Toll-like receptor signaling pathway in melanoma

Abstract

Melanoma is a malignant tumor of melanocytes and is often considered immunogenic cancer. Toll-like receptor-related genes are expressed differently in most types of cancer, depending on the immune microenvironment inside cancer, and the key function of Toll-like receptors (TLRs) for melanoma has not been fully elucidated. Based on multi-omics data from TCGA and GEO databases, we first performed pan-cancer analysis on TLR, including CNV, SNV, and mRNA changes in TLR-related genes in multiple human cancers, as well as patient prognosis characterization. Then, we divided melanoma patients into three subgroups (clusters 1, 2, and 3) according to the expression of the TLR pathway, and explored the correlation between TLR pathway and melanoma prognosis, immune infiltration, metabolic reprogramming, and oncogene expression characteristics. Finally, through univariate Cox regression analysis and LASSO algorithm, we selected six TLR-related genes to construct a survival prognostic model, divided melanoma patients into the training set, internal validation set 1, internal validation set 2, and external validation set for multiple validations, and discussed the correlation between model genes and clinical features of melanoma patients. In conclusion, we constructed a prognostic survival model based on TLR-related genes that precisely and independently demonstrated the potential to assess the prognosis and immune traits of melanoma patients, which is critical for patients’ survival.

Exploring Regorafenib Responsiveness and Uncovering Molecular Mechanisms in Recurrent Glioblastoma Tumors through Longitudinal In Vitro Sampling

“…To elucidate pathways associated with DEGsA and DEGsB, we conducted a comprehensive analysis using the Reactome database. DEGsA primarily engage in attenuating/negatively regulating MAP kinase (ERK/MAPK) signaling pathways, interleukin-17 signaling, Toll-like receptor (TLR) cascades, and signaling by receptor tyrosine kinases (RTKs), potentially contributing to drug response mechanisms to REGO [ 57 , 58 ]. DEGsB focus on transcriptional regulation by E2F6, metabolic processes, membrane trafficking, and cell cycle regulation during the G2/M transition [ 59 ].…”

Comprehensive pan-cancer analysis of inflammatory age-clock-related genes as prognostic and immunity markers based on multi-omics data

“…Thus, integrating multi-omics data may identify the role of iAge-CRGs in different tumors more comprehensively. In this study, we analyzed changes in genes, such as gene expression changes, single nucleotide changes (SNVs), variations in gene copies (CNVs), and gene methylation status changes 26 . Additionally, we considered patients’ response to medications and the infiltration levels of 24 diverse immune cell types 27 .…”

Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer

“…D) The association between each parthanatos-related gene and the GC immune microenvironment was calculated. Based on previous literature reports [ 34 ], we identified a set of 29 genes related to immune cells and immune-related functions. The ssGSEA algorithm was used to evaluate the immune cell and immune function scores of 743 GC samples, and Spearman correlation analysis was performed to explore the potential association between each parthanatos-related gene and immune cell infiltration and immune function.…”