Research Paper Volume 13, Issue 9 pp 12896—12918

Identification of a novel glycolysis-related gene signature for predicting the prognosis of osteosarcoma patients

Mengkai Yang1, *, , Xiaojun Ma1, *, , Zhuoying Wang1, , Tao Zhang1, &, , Yingqi Hua1, , Zhengdong Cai1, ,

  • 1 Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
* Equal contribution

Received: September 21, 2020       Accepted: March 2, 2021       Published: May 5, 2021
How to Cite

Copyright: © 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


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.