Development of a prognostic index and screening of prognosis related genes based on an immunogenomic landscape analysis of bladder cancer

Abstract

Background: Bladder cancer (BLCA) is one of the most common urinary tract malignant tumors. It is associated with poor outcomes, and its etiology and pathogenesis are not fully understood. There is great hope for immunotherapy in treating many malignant tumors; therefore, it is worthwhile to explore the use of immunotherapy for BLCA.Methods: Gene expression profiles and clinical information were obtained from The Cancer Genome Atlas (TCGA), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal. Differentially-expressed and survival-associated IRGs in patients with BLCA were identified using computational algorithms and Cox regression analysis. We also performed functional enrichment analysis. Based on IRGs, we employed multivariate Cox analysis to develop a new prognostic index.Results: We identified 261 IRGs that were differentially expressed between BLCA tissue and adjacent tissue, 30 of which were significantly associated with the overall survival (all P<0.01). According to multivariate Cox analysis, nine survival-related IRGs (MMP9, PDGFRA, AHNAK, OAS1, OLR1, RAC3, IGF1, PGF, and SH3BP2) were high-risk genes. We developed a prognostic index based on these IRGs and found it accurately predicted BLCA outcomes associated with the TNM stage. Intriguingly, the IRG-based prognostic index reflected infiltration of macrophages.Conclusions: An independent IRG-based prognostic index provides a practical approach for assessing patients' immune status and prognosis with BLCA. This index independently predicted outcomes of BLCA.

Comprehensive Exploration of Tumor Microenvironment Modulation Based on the ESTIMATE Algorithm in Bladder Urothelial Carcinoma Microenvironment

“…In this study, we found that IGF1 may contribute to an increase in the levels of native B cell and M2 macrophages. MMP9, as a classical immune-related gene, has been demonstrated to play a vital role in the immune treatment of BLCA ( 28 ). MMP9 contributes to the promotion of the neutrophil-mediated inflammation, indicating its roles in immune infiltrates ( 29 ).…”

A Prognostic Model for Predicting Tumor Mutation Burden and Tumor-Infiltrating Immune Cells in Bladder Urothelial Carcinoma

“…Previous studies have shown that OAS1 could suppress accumulation of excess Poly (ADPribose) (PAR) in response to DNA damage, thereby inhibiting programmed cell death due to energy depletion and/or activation of PAR (Kondratova et al, 2020). Moreover, Qu and colleagues once proposed a IRG-based prognostic index containing AHNAK and OAS1 that could assess immune status and prognosis with BLCA (Qu et al, 2021). Besides, NGF is a member of the neurotrophic factor family that protects peripheral nerve cells (Rocco et al, 2018).…”

Controlling Nutritional Status Score Before Receiving Treatment as a Prognostic Indicator for Patients With Urothelial Cancer: An Exploration Evaluation Methods

“…( 5) the effects of the low CONUT group and high CONUT group on the prognosis of surgical patients were discussed, and the hazard ratio (HR) was provided. (6) the design type of the study is a retrospective study and prospective study. (7) the research, which is rated as high quality by the study quality evaluation system.…”

“…Any pathological type of bladder cancer has a recurrence, fatal complications, and poor prognosis after treatment. At present, a lot of studies have proved that some genes, the ratio of fibrinogen to serum albumin, the percentage of neutrophils to lymphocytes, and the modified Glasgow Prognostic Score (GPS) can be used to assess the prognosis of BC (5)(6)(7). UTUC includes ureteral cancer and renal pelvic cancer, with a low incidence, accounting for less than 10% of urothelial cancers.…”