A novel angiogenesis-based molecular signature related to prognosis and tumor immune interactions of pancreatic cancer

Abstract

Angiogenesis, a hallmark of cancer, is related to prognosis, tumor progression, and treatment response. Nevertheless, the correlation of angiogenesis-based molecular signature with clinical outcome and immune cell infiltration has not been thoroughly studied in pancreatic cancer. In this study, multiple bioinformatics methods were combined to evaluate prognosis, immune cell infiltration, and the alterations of angiogenesis-related genes (ARGs) in PC samples, and further establish a novel angiogenesis-related gene signature. Moreover, the protein and mRNA expression levels of four angiogenesis risk genes were determined by Human Protein Atlas (HPA) database and qPCR analysis, respectively. Here, we recognized two distinct angiogenesis subtypes and two gene subtypes, and revealed the critical roles of ARGs in the tumor immune microenvironment (TIME), clinical features, and prognosis. Consequently, we established an ARGs score to predict prognosis and therapeutic response of PC patients, and validated its robust predictive ability. Additionally, the ARGs score was markedly associated with clinical outcomes, tumor mutation burden (TMB), and chemotherapeutic drug sensitivity. In brief, our findings imply that the ARGs score is a robust prognostic indicator and may contribute to the development of effective individualized therapies for PC.

Identification of gene signatures related to hypoxia and angiogenesis in pancreatic cancer to aid immunotherapy and prognosis

“…The hypoxic prognostic model (HPM) was constructed as follows (1): review the literature through pubmed website to obtain hypoxia-related genes (2); take the intersection of hypoxiarelated genes and PC DEG (3); sequentially construct HPM by univariate Cox, last absolute shrinkage and selection operator (LASSO), multivariate Cox analysis was performed to construct HPM (4); calculate the patient's risk score calculated according to the prognostic model (5); divide patients into high and low risk groups based on the median value of the risk score (6); assess the prognostic efficacy of the prognostic model though Kaplan-Meier (KM) survival curve and receiver operating characteristic (ROC) curve. The angiogenic prognostic model (APM) was created in a way that was consistent with HPM.…”

“…One of the traits of cancer is angiogenesis, a process that facilitates rapid tumor development, allows for remote tumor spread, and feeds tumor tissue with the oxygen and nutrients needed for metabolism ( 4 ). Angiogenesis is one of the major contributors in tumor growth, infiltration and metastasis ( 5 ). Neovascularization, which develops inside tumor tissues and feeds tumor cells with nutrients, causes a rapid rise in the number of tumor cells, their volume, their infiltration of nearby tissues, and their propensity to metastasize ( 6 ).…”