Angiogenesis Pathway in Kidney Renal Clear Cell Carcinoma and Its Prognostic Value for Cancer Risk Prediction

Abstract

Angiogenesis, a process highly regulated by pro-angiogenic and anti-angiogenic factors, is disrupted and dysregulated in cancer. Despite the increased clinical use of angiogenesis inhibitors in cancer therapy, most molecularly targeted drugs have been less effective than expected. Therefore, an in-depth exploration of the angiogenesis pathway is warranted. In this study, the expression of angiogenesis-related genes in various cancers was explored using The Cancer Genome Atlas datasets, whereupon it was found that most of them were protective genes in the patients with kidney renal clear cell carcinoma (KIRC). We divided the samples from the KIRC dataset into three clusters according to the mRNA expression levels of these genes, with the enrichment scores being in the order of Cluster 2 (upregulated expression) > Cluster 3 (normal expression) > Cluster 1 (downregulated expression). The survival curves plotted for the three clusters revealed that the patients in Cluster 2 had the highest overall survival rates. Via a sensitivity analysis of the drugs listed on the Genomics of Drug Sensitivity in Cancer database, we generated IC50 estimates for 12 commonly used molecularly targeted drugs for KIRC in the three clusters, which can provide a more personalized treatment plan for the patients according to angiogenesis-related gene expression. Subsequently, we investigated the correlation between the angiogenesis pathway and classical cancer-related genes as well as that between the angiogenesis score and immune cell infiltration. Finally, we used the least absolute shrinkage and selection operator (LASSO)–Cox regression analysis to construct a risk score model for predicting the survival of patients with KIRC. According to the areas under the receiver operating characteristic (ROC) curves, this new survival model based on the angiogenesis-related genes had high prognostic prediction value. Our results should provide new avenues for the clinical diagnosis and treatment of patients with KIRC.

An integrated analysis revealing the angiogenic function of TP53I11 in tumor microenvironment

“…To elucidate the correlation between TP53I11 and vascular endothelial cells, we employed the Lung Tumor ECTax database [ 28 ], a robust resource facilitating the exploration of gene expression within endothelial cell subtypes. Utilizing the clustering and grouping annotations from the original author, we reconfigured visualizations to depict the distribution of vascular endothelial cell subtypes ( Fig.…”

“…However, notably, KIRC exhibited a more favorable prognosis. Che et al conducted bioinformatics research to explore the relationship between angiogenesis-related genes and KIRC [ 28 ]. They observed that, unlike in other tumors (such as UCEC and KICH), most angiogenesis-related genes in patients with KIRC acted as protective factors [ 28 ].…”

Comprehensive characterization of extracellular matrix-related genes in PAAD identified a novel prognostic panel related to clinical outcomes and immune microenvironment: A silico analysis with in vivo and vitro validation

“…These enzymes are responsible for catalyzing the elimination of acetyl groups from histone and non-histone lysine residues and are intimately linked to tumor onset and metastasis ( 18 ). Recently, suppression of HDAC has emerged as a method that has been verified in clinical practice for treating cancer ( 19 ). The levels of expression of HDAC1, HDAC7, and HDAC9 were found to be considerably lowered in C2 contrasted with the levels observed in C1 ( Figure 7B ).…”

The clinical significance, immune infiltration, and tumor mutational burden of angiogenesis-associated lncRNAs in kidney renal clear cell carcinoma

“…It is critical to explore the potential predictor for KIRC treatment and prognosis. Angiogenesis is a complex consequence of co-regulation between pro-angiogenic and anti-angiogenic factors, and it is disrupted and dysregulated in cancer ( 33 ). Angiogenesis is an important process in cancer pathogenesis and therapy.…”