Exploration of various roles of hypoxia genes in osteosarcoma

Abstract

Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.

Ferroptosis defense mechanisms: The future and hope for treating osteosarcoma

“…overall survival in OS. [131][132][133][134] Ma et al 135 screened and analyzed hypoxia-related genes SLC2A1 and FBP1 in OS patients. In addition to SLC2A1 and FBP1, three ferroptosis-related genes-AKR1C2, AKR1C1, and ALOX15-were first proposed to be associated with hypoxia in OS cells.…”

“…Some of these genes have been validated as potential targets for OS therapy via ferroptosis immunotherapy and prognosis improvement, providing new insights and directions for understanding the molecular mechanisms and overall survival in OS 131–134 . Ma et al 135 screened and analyzed hypoxia‐related genes SLC2A1 and FBP1 in OS patients. In addition to SLC2A1 and FBP1, three ferroptosis‐related genes—AKR1C2, AKR1C1, and ALOX15—were first proposed to be associated with hypoxia in OS cells.…”