Abstract
Osteosarcoma (OS) is a prevalent invasive bone cancer, with numerous homeobox family genes implicated in tumor progression. This study aimed to develop a prognostic model using HOX family genes to assess osteosarcoma patient outcomes. Data from osteosarcoma patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were collected. LASSO regression and multivariate COX regression analyses were employed to create and validate a risk-prognosis model in a validation cohort. Four genes (HOXA1, HOXA5, HOXA6, HOXA13) were identified to construct the risk-prognosis model. Patients were categorized into high-risk and low-risk groups, with significantly better prognosis observed in the low-risk group. A nomogram was developed to predict patients' overall survival. Variances in gene function were primarily concentrated in immune-related pathways. ssGSEA indicated that immune cell content and function were relatively deficient in the high-risk group. Notably, HOXA1 overexpression suppressed osteosarcoma cell proliferation, migration, invasion, and tumor growth. The model exhibited high accuracy and versatility, enhancing early diagnosis rates and aiding clinicians in decision-making and personalized treatment.