Objective. This study aimed to develop a novel ferroptosis-related gene-based prognostic signature for esophageal carcinoma (ESCA). Methods. The TCGA-ESCA gene expression profiles and corresponding clinical data were downloaded from the TCGA database. Ferroptosis-related genes were identified from the literature and public databases, which were intersected with the differentially expressed genes between ESCA and normal samples. After univariate Cox regression and random forest analyses, several ferroptosis-related feature genes were identified and used to construct a prognostic signature. Then, the prognostic value of the complex value and the correlation of the complex value with immune cell infiltration were analyzed. Moreover, function analysis, mutation analysis, and molecular docking on the ferroptosis-related feature genes were performed. Results. Based on the TCGA dataset and ferroptosis pathway genes, 1929 ferroptosis-related genes were preliminarily selected. Following univariate Cox regression analysis and survival analysis, 14 genes were obtained. Then, random forest analysis identified 10 ferroptosis key genes. These 10 genes were used to construct a prognostic complex value. It was found that low complex value indicated better prognosis compared with high complex value. In different ESCA datasets, there were similar differences in the proportion of immune cell distribution between the high and low complex value groups. Furthermore, TNKS1BP1, AC019100.7, KRI1, BCAP31, and RP11-408E5.5 were significantly correlated with ESCA tumor location, lymph node metastasis, and age of patients. KRI1 had the highest mutation frequency. BCAP31 had the strongest binding ability with small molecules DB12830, DB05812, and DB07307. Conclusion. We constructed a novel ferroptosis-related gene signature, which has the potential to predict patient survival and tumor-infiltrating immune cells of ESCA.

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.