Research Paper Volume 13, Issue 9 pp 12896—12918
Identification of a novel glycolysis-related gene signature for predicting the prognosis of osteosarcoma patients
- 1 Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
Received: September 21, 2020 Accepted: March 2, 2021 Published: May 5, 2021
https://doi.org/10.18632/aging.202958How to Cite
Abstract
Glycolysis ensures energy supply to cancer cells, thereby facilitating tumor progression. Here, we identified glycolysis-related genes that could predict the prognosis of patients with osteosarcoma. We examined 198 glycolysis-related genes that showed differential expression in metastatic and non-metastatic osteosarcoma samples in the TARGET database, and identified three genes (P4HA1, ABCB6, and STC2) for the establishment of a risk signature. Based on the signature, patients in the high-risk group had poor outcomes. An independent Gene Expression Omnibus database GSE21257 was selected as the validation cohort. Receiver operating characteristic curve analysis was performed and the accuracy of predicting the 1- and 3-year survival rates was shown by the areas under the curve. The results were 0.884 and 0.790 in the TARGET database, and 0.740 and 0.759 in the GSE21257, respectively. Furthermore, we applied ESTIMATE algorithm and performed single sample gene set enrichment analysis to compare tumor immunity between high- and low-risk groups. We found that the low-risk group had higher immune scores and immune infiltration levels than the high-risk group. Finally, we chose P4HA1 as a representative gene to verify the function of risk genes in vitro and in vivo and found that P4HA1 could promote the metastasis of osteosarcoma cells. Our study established a novel glycolysis-related risk signature that could predict the prognosis of patients with osteosarcoma.
Abbreviations
OS: osteosarcoma; P4HA1: Prolyl 4-Hydroxylase Subunit Alpha 1; STC2: Stanniocalcin 2; ABCB6: ATP Binding Cassette Subfamily B Member 6; GSEA: Gene set enrichment analysis; TARGET: Therapeutically Applicable Research to Generate Effective Treatments; GEO: Gene Expression Omnibus; TIICs: Tumor-infiltrating immune cells; ROC: Receiver Operating Characteristic.