Identification and Development of an Age-Related Classification and Signature to Predict Prognosis and Immune Landscape in Osteosarcoma

Abstract

Background. In childhood and adolescence, the prevailing bone tumor is osteosarcoma associated with frequent recurrence and lung metastasis. This research focused on predicting the survival and immune landscape of osteosarcoma by developing a prognostic signature and establishing aging-related genes (ARGs) subtypes. Methods. The training group comprised of the transcriptomic and associated clinical data of 84 patients with osteosarcoma accessed at the TARGET database and the validation group consisted of 53 patients from GSE21257. The aging-related subtypes were identified using unsupervised consensus clustering analysis. The ARG signature was developed utilizing multivariate Cox analysis and LASSO regression. The prognostic value was assessed using the univariate and multivariate Cox analyses, Kaplan-Meier plotter, time-dependent ROC curve, and nomogram. The functional enrichment analyses were performed by GSEA, GO, and KEGG analysis, while the ssGSEA, ESTIMATE, and CIBERSORT analyses were conducted to reveal the immune landscape in osteosarcoma. Results. The two clusters of osteosarcoma patients formed based on 543 ARGs, depicted a considerable difference in the tumor microenvironment, and the overall survival and immune cell infiltration rate varied as well. Among these, the selected 23 ARGs were utilized for the construction of an efficient predictive prognostic signature for the overall survival prediction. The testing in the validation group of osteosarcoma patients confirmed the status of the high-risk score as an independent indicator for poor prognosis, which was already identified as such using the univariate and multivariate Cox analyses. Furthermore, the ARG signature could distinguish different immune-related functions, infiltration status of immune cells, and tumor microenvironment, as well as predict the immunotherapy response of osteosarcoma patients. Conclusion. The aging-related subtypes were identified and a prognostic signature was developed in this research, which determined different prognoses and allowed for treatment of osteosarcoma patients to be tailored. Additionally, the immunotherapeutic response of individuals with osteosarcoma could also be predicted by the ARG signature.

Comprehensive genomics analysis of aging related gene signature to predict the prognosis and drug resistance of colon adenocarcinoma

“…Cellular senescence has been studied in various cancer types and compelling evidences have revealed that cellular senescence is associated with cancer prognosis (Dai et al, 2022a;Domen et al, 2022a;Domen et al, 2022b). Development of senescence-related classification and characterization of senescence-based signature have attracted much attention in tumor research (Feng et al, 2022a;Hong et al, 2022). However, the mechanisms of cellular senescence in COAD, as well as the specific prognostic signatures are poorly understood.…”