A novel immune cell signature for predicting osteosarcoma prognosis and guiding therapy

Abstract

Dysregulation of immune cell infiltration in the tumor microenvironment contributes to the progression of osteosarcoma (OS). In the present study, we explored genes related to immune cell infiltration and constructed a risk model to predict the prognosis of and guide therapeutic strategies for OS. The gene expression profile of OS was obtained from TARGET and Gene Expression Omnibus, which were set as the discovery and verification cohorts. CIBERSORT and Kaplan survival analyses were used to analyze the effects of immune cells on the overall survival rates of OS in the discovery cohort. Differentially expressed gene (DEG) analysis and protein–protein interaction (PPI) networks were used to analyze genes associated with immune cell infiltration. Cox regression analysis was used to select key genes to construct a risk model that classified OS tissues into high- and low-risk groups. The prognostic value of the risk model for survival and metastasis was analyzed by Kaplan–Meier survival analyses, receiver operating characteristic curves, and immunohistochemical experiments. Immunological characteristics and response effects of immune checkpoint blockade (ICB) therapy in OS tissues were analyzed using the ESTIMATE and Tumor Immune Dysfunction and Exclusion algorithms, while sensitivity for both targeted and chemotherapy drugs was analyzed using the OncoPredict algorithm. It was demonstrated that the high infiltration of resting dendritic cells in OS tissues was associated with poor prognosis. A total of 225 DEGs were found between the high- and low-infiltration groups of OS tissues, while 94 genes interacted with others. Through COX analyses, among these 94 genes, four genes (including AOC3, CDK6, COL22A1, and RNASE6) were used to construct a risk model. This risk model showed a remarkable prognostic value for survival rates and metastasis in both the discovery and verification cohorts. Even though a high microsatellite instability score was observed in the high-risk group, the ICB response in the high-risk group was poor. Furthermore, using OncoPredict, we found that the high-risk group OS tissues were resistant to seven drugs and sensitive to 25 drugs. Therefore, our study indicates that the resting dendritic cell signature constructed by AOC3, CDK6, COL22A1, and RNASE6 may contribute to predicting osteosarcoma prognosis and thus therapy guidance.

Coordinating single‐cell and bulk RNA‐seq in deciphering the intratumoral immune landscape and prognostic stratification of prostate cancer patients

“…The cells were then further divided into Histone‐high score (Histone‐H) and Histone‐low score (Histone‐L) groups based on their respective scores. Differentially expressed genes (DEGs) were identified via Seruat and Limma R package between Histone‐H and Histone‐L groups, with thresholds of false discovery rate (FDR) values <.05 and |log 2 fold change (FC)| ≥ 1 15 . Furthermore, to examine the differences between two CTC subsets, we calculated GSVA scores for 50 tumor‐related pathways of Hallmark.…”

“…Differentially expressed genes (DEGs) were identified via Seruat and Limma R package between Histone-H and Histone-L groups, with thresholds of false discovery rate (FDR) values <.05 and jlog 2 fold change (FC)j ≥ 1. 15 Furthermore, to examine the differences between two CTC subsets, we calculated GSVA scores for 50 tumor-related pathways of Hallmark. PROGENy algorithm was utilized to calculate the pathway activity score between groups.…”

Inflammasome‐related gene signatures as prognostic biomarkers in osteosarcoma

“…Understanding the dance between osteosarcoma cells and the immune system reveals a landscape rife with potential targets for intervention 16 . The immune system, traditionally viewed as an army defending against the onslaught of neoplastic transformation, has been found to be co‐opted at times, aiding and abetting tumour growth and spread 17,18 . Chronic inflammation, a hallmark of immune involvement, has been linked to various stages of tumorigenesis, from initiation to metastasis, presenting a challenging yet critical target for therapeutic development 19 …”

“…16 The immune system, traditionally viewed as an army defending against the onslaught of neoplastic transformation, has been found to be co-opted at times, aiding and abetting tumour growth and spread. 17,18 Chronic inflammation, a hallmark of immune involvement, has been linked to various stages of tumorigenesis, from initiation to metastasis, presenting a challenging yet critical target for therapeutic development. 19 The heterogeneity of osteosarcoma at the molecular level presents both a challenge and an opportunity for researchers.…”

A risk model based on the tumor infiltrating CD8+T cells correlated with the prognosis and therapy in bladder urothelial carcinoma

“…In recognition of foreign antigens, CD8 + T cells can induce apoptosis by releasing cytotoxins or expressing death ligands on the cell surface,which is a key determinant of good clinical outcomes in many tumors [16][17]. In recent years, with the progress of transcriptome sequencing technology, several immune cell types have been found to be involved in various tumors, which correlates with prognosis and therapy [12,18].…”