Identification of endothelial-related molecular subtypes for bladder cancer patients

Abstract

BackgroundBladder cancer (BC) is a disease with significant heterogeneity and poor prognosis. The prognosis and therapeutic response of BC patients are significantly influenced by endothelial cells in the tumor microenvironment. In order to understand BC from the perspective of endothelial cells, we orchestrated molecular subtypes and identified key genes.MethodsSingle-cell and bulk RNA sequencing data were extracted from online databases. R and its relative packages were used to analyze these data. Cluster analysis, prognostic value analysis, function analysis, immune checkpoints, tumor immune environment and immune prediction were conducted.ResultsFive endothelial-related genes (CYTL1, FAM43A, HSPG2, RBP7, and TCF4) divided BC patients in the TCGA, GSE13507, and GSE32894 datasets into two clusters, respectively. In prognostic value analysis, patients in the cluster 2 were substantially associated with worse overall survival than those in the cluster 1 according to the results of TCGA, GSE13507 and GSE32894 datasets. In the results of functional analysis, the endothelial-related clusters was enriched in immune-related, endothelial-related and metabolism-related pathways. Samples in the cluster 1 had a statistically significant increase in CD4+ T cells and NK-cell infiltration. Cluster 1 was positively correlated with the cancer stem score and tumor mutational burden score. The results of immune prediction analysis indicated that 50.6% (119/235) of patients in the cluster 1 responded to immunotherapy, while the response rate in the cluster 2 decreased to 16.7% (26/155).ConclusionIn this study, we categorized and discovered distinctive prognosis-related molecular subtypes and key genes from the perspective of endothelial cells at the genetic level by integrating single-cell and bulk RNA sequencing data, primarily to provide a roadmap for precision medicine.

Prognostic significance and immune landscape of a cell cycle progression-related risk model in bladder cancer

“…A concentrated effort has been made over the last thirty years to investigate novel therapeutic, prognostic, and diagnostic biomarkers for BCa patients in an attempt to determine which patients could benefit the most from treatment. Individual or combined genomes that identify unique patterns of gene expression inside disease processes have been found to be useful for prognostic prediction and disease classification [ 36 , 37 ]. Anomalies in a number of cellular pathways, most notably the disruption of cell cycle control, are thought to play a role in the carcinogenesis and development of BCa [ 38 , 39 ].…”

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma

“…In addition, the accumulation of lactic acid in tumors is achieved by inhibiting PHD2 and activating HIF1-α and NF-κB, and to a large extent, it contributes to the angiogenesis phenotype ( 41 ). The driving force of lactic acid promoting angiogenesis provides new therapeutic options without the drawbacks of traditional anti-angiogenic drugs for ccRCC ( 42 , 43 ). Interestingly, despite such high lactate dehydrogenase activity in T cells and MKI67 + macrophages, there is an apparent lack of lactate metabolic processes.…”

Adhesion-regulating molecule 1 (ADRM1) can be a potential biomarker and target for bladder cancer

“…In high ADRM1 expression group, the expression of PD-L1 and PD-1 increased, suggesting that patients with high ADRM1 expression were more likely to benefit from anti-PD-L1 therapy. The tumor microenvironment plays a vital role in immunotherapy 47 , 48 . In the aspect of infiltrating immune cells, the high ADRM1 group contained significantly higher proportion of CD8 + T cells and Macrophage (M1), and lower proportion of CD4 + T memory cells and Mast cells.…”