Identification and validation of an anoikis-associated gene signature to predict clinical character, stemness, IDH mutation, and immune filtration in glioblastoma

Abstract

BackgroundGlioblastoma (GBM) is the most prominent and aggressive primary brain tumor in adults. Anoikis is a specific form of programmed cell death that plays a key role in tumor invasion and metastasis. The presence of anti-anoikis factors is associated with tumor aggressiveness and drug resistance.MethodsThe non-negative matrix factorization algorithm was used for effective dimension reduction for integrated datasets. Differences in the tumor microenvironment (TME), stemness indices, and clinical characteristics between the two clusters were analyzed. Difference analysis, weighted gene coexpression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator regression were leveraged to screen prognosis-related genes and construct a risk score model. Immunohistochemistry was performed to evaluate the expression of representative genes in clinical specimens. The relationship between the risk score and the TME, stemness, clinical traits, and immunotherapy response was assessed in GBM and pancancer.ResultsTwo definite clusters were identified on the basis of anoikis-related gene expression. Patients with GBM assigned to C1 were characterized by shortened overall survival, higher suppressive immune infiltration levels, and lower stemness indices. We further constructed a risk scoring model to quantify the regulatory patterns of anoikis-related genes. The higher risk score group was characterized by a poor prognosis, the infiltration of suppressive immune cells and a differentiated phenotype, whereas the lower risk score group exhibited the opposite effects. In addition, patients in the lower risk score group exhibited a higher frequency of isocitrate dehydrogenase (IDH) mutations and a more sensitive response to immunotherapy. Drug sensitivity analysis was performed, revealing that the higher risk group may benefit more from drugs targeting the PI3K/mTOR signaling pathway.ConclusionWe revealed potential relationships between anoikis-related genes and clinical features, TME, stemness, IDH mutation, and immunotherapy and elucidated their therapeutic value.

An anoikis-based signature for predicting prognosis in hepatocellular carcinoma with machine learning

“…HCC is a highly life-threatening malignancy, and effective predictive biomarkers of HCC are still lacking. Recently, an increasing number of studies have demonstrated alterations of anoikis regulators and their significant role in tumorigenesis and progression in various malignancies, including lung cancer, prostate cancer, breast cancer and glioblastoma ( Jin et al, 2018 ; Tajbakhsh et al, 2019 ; Du et al, 2021 ; Sun et al, 2022 ; Yu et al, 2022 ). However, the underlying mechanisms and prognostic value of dysregulated anoikis-related genes in HCC remain unclear.…”

Identification of a novel anoikis‐related gene signature to predict prognosis and tumor microenvironment in lung adenocarcinoma

“… 10 In addition, ARGs have been proven to be associated with prognosis in several tumors. 11 , 12 , 13 However, the comprehensive analyses of the implications of anoikis in LUAD are still scarce. Therefore, identification of the predominant genes related to anoikis with prognostic significance in LUAD is vital.…”

“…In another study by D'Amato et al, TDO2 was found as an attractive factor to facilitate anoikis resistance in triple‐negative breast cancer 10 . In addition, ARGs have been proven to be associated with prognosis in several tumors 11–13 . However, the comprehensive analyses of the implications of anoikis in LUAD are still scarce.…”

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

“…Anoikis, as a programmed cell death, is a potential barrier to cancer cell metastasis. Previous studies have pointed that the epithelial or endothelial cells detached from extracellular matrix (ECM) succumb to classical apoptosis commonly known as anoikis ( Chi et al, 2022 ; Sun et al, 2022 ). Evasion from apoptosis is one of the essential changes in the malignant transformation of cells.…”