Anoikis-related genes signature development for kidney renal clear cell carcinoma prognosis and tumor microenvironment

Abstract

Abstract Kidney renal clear cell carcinoma (KIRC) is one of the most common primary malignancies of the urinary tract, highly heterogeneous, and increasing in incidence worldwide. Anoikis is a specific type of programmed cell death in which solid tumor cells or normal epithelial cells that do not have metastatic properties lose adhesion to the extracellular matrix (ECM) or undergo inappropriate cell adhesion-induced apoptosis. Anoikis is thought to play a critical role in tumorigenesis, maintenance, and treatment, according to an increasing amount of research. However, there is still some uncertainty regarding the general impact of anoikis-related genes (ARGs) on the prognostic importance, tumor microenvironment (TME) characteristics, and treatment reaction of KIRC patients. For this study, we used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets to access the RNA sequencing results and clinical information from KIRC patients. 29 ARGs related to survival were found using differential analysis and univariate Cox regression analysis. The samples were then divided into two clusters that had different immune traits via unsupervised cluster analysis using 29 prognosis-associated differently expressed ARGs. Then, to build an ARGs signature, 7 genes (PLAU, EDA2R, AFP, PLG, TUBB3, APOBEC3G, and MALAT1) were found using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The new ARGs signature demonstrated outstanding prognostic capability for KIRC patients' overall survival (OS). On the basis of the clinical parameters (gender, tumor grade, age, and stage) and the ARGs risk score, a clinical nomogram was created. This nomogram demonstrated excellent predictive value. In addition, patients that were categorized based on risk ratings also exhibited distinguishing immunological traits and medication sensitivity. In conclusion, for KIRC patients, we created an ARGs signature that strongly connects to immunological traits and therapy response. Clinicians may find this ARGs signature helpful in developing more individualized and detailed treatment strategies for KIRC patients.