Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

Abstract

Osteosarcoma is the most frequent bone tumor. Notwithstanding that significant medical progress has been achieved in recent years, the 5-year overall survival of osteosarcoma patients is inferior. Regulation of fatty acids and lactate plays an essential role in cancer metabolism. Therefore, our study aimed to comprehensively assess the fatty acid and lactate metabolism pattern and construct a fatty acid and lactate metabolism–related risk score system to predict prognosis in osteosarcoma patients. Clinical data and RNA expression data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We used the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic risk score model. Relationships between the risk score model and age, gender, tumor microenvironment characteristics, and drug sensitivity were also explored by correlation analysis. We determined the expression levels of prognostic genes in osteosarcoma cells via Western blotting. We developed an unknown fatty acid and lactate metabolism–related risk score system based on three fatty acid and lactate metabolism–related genes (SLC7A7, MYC, and ACSS2). Survival analysis showed that osteosarcoma patients in the low-risk group were likely to have a better survival time than those in the high-risk group. The area under the curve (AUC) value shows that our risk score model performs well in predicting prognosis. Elevated fatty acids and lactate risk scores weaken immune function and the environment of the body, which causes osteosarcoma patients’ poor survival outcomes. In general, the constructed fatty acid and lactate metabolism–related risk score model can offer essential insights into subsequent mechanisms in available research. In addition, our study may provide rational treatment strategies for clinicians based on immune correlation analysis and drug sensitivity in the future.

Dissecting the role of lactate metabolism LncRNAs in the progression and immune microenvironment of osteosarcoma

“…Wu et al. [66] selected fatty acid and lactate metabolism-related genes to construct a prognostic prediction model that also had a significant effect on the tumor immune microenvironment, which had similarities with our study, but it is worth discussing that our study focused on a finer perspective of lactate metabolism and limited to lncRNAs, a popular target for a variety of cancers, to construct a prognostic prediction model with higher diagnostic value. The AUC values for predicting 1-, 3-, and 5-year survival in osteosarcoma reached 0.943, 0.927, and 0.947, respectively, compared with only 0.841, 0.750, and 0.750, respectively, in the model of Wu et al.…”

Multifunctional nanomaterials via cell cuproptosis and oxidative stress for treating osteosarcoma and OS-induced bone destruction

“…7 G). The most lethal disaster and clinical problem for patient survival rate in OS is lung metastases [ 48 ]. The anti-metastasis effect of the biomaterials was assessed using pulmonary bioluminescence imaging and H&E staining.…”

Targeting ACSS2 activity suspends the formation of chemoresistance through suppressed histone H3 acetylation in human breast cancer

“…In contrast to cells in normal tissues, tumor cells within tumors exhibit unrestrained growth, dysregulated differentiation, and senescence resistance, necessitating adaptation to uctuations in nutrient, carbon source, and oxygen supply in their environment. While the expression level and role of ACSS2 in tumor progression, including BC cells, remain controversial, there is consensus that lipid metabolism involving ACSS2 and its synthesis of acetyl-CoA directly impacts the survival and invasion of tumor cells [18][19][20][26][27][28][29][30]. Studies on breast ductal carcinoma cells have revealed that increased ACSS2 expression, triggered by insu cient oxygen supply, is regulated by the combined action of SREBP2 and HIF.…”

“…While the in uence of ACSS2 levels on cancer progression remains controversial to some extent, clinical data predominantly associate its upregulation with poor prognosis in multiple cancer patients [26][27][28][29][30]. In BC, ACSS2 levels have been reported to be lower than in mammary broma tissues.…”