ABSTRACT
Immune-modulating therapies exhibit abundant promise compared to traditional treatment for osteosarcoma. We aim to establish an immune-related prognostic signatures in osteosarcoma. We identified the differentially expressed genes in osteosarcoma compared with normal controls using the GEO dataset. The intersection with immune-related genes was considered as differentially expressed immune genes. Potential prognosis-related differentially expressed genes were first analyzed with the multifactor Cox regression and then the step function performed the iteration. The best model was finally chosen as the immunological risk score signature model. And finally, we evaluated the correlation of genes in the prognostic model with immune cells, common immune checkpoints, and immune checkpoint blockade responses. We identified 1527 significantly upregulated and 2407 significantly downregulated genes in osteosarcoma compared to normal samples. In the 258 differentially expressed immune genes, 20 genes with independent prognostic significance were included in the step function. Finally, we constructed a prognostic signature for overall survival based on five immune genes (JAG2, PLXNB1, CMKLR1, NUDT6, and PSMC4) in osteosarcoma. These five genes are closely related to immune infiltration. Osteosarcoma with high JAG2 expression or low CMKLR1 expression may be associated with better immune checkpoint blockade response. JAG2 overexpression or CMKLR1 inhibition induced sensitivity to PD-1 antibody in osteosarcoma cells. We constructed a prognosis prediction signature containing five immune-related genes (JAG2, PLXNB1, CMKLR1, NUDT6, and PSMC4) with a significant prognostic value in osteosarcoma. Significant differences in immune infiltration and immunotherapy responses were identified between groups with different levels of these genes.
ABSTRACT
Osteoarthitis (OA) is the most common aging-related joint pathology; the aging process results in changes to joint tissues that ultimately contribute to the development of OA. Articular chondrocytes exhibit an aging-related decline in their proliferative and synthetic capacity. Sirtuin 1 (SIRT 1), a longevity gene related to many diseases associated with aging, is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and master metabolic regulator. Along with its natural activator resveratrol, SIRT 1 actively participates in the OA pathological progress. SIRT 1 expression in osteoarthritic cartilage decreases in the disease progression of OA; it appears to play a predominantly regulatory role in OA. SIRT 1 can regulate the expression of extracellular matrix (ECM)-related proteins; promote mesenchymal stem cell differentiation; play anti-catabolic, anti-inflammatory, anti-oxidative stress, and anti-apoptosis roles; participate in the autophagic process; and regulate bone homeostasis in OA. Resveratrol can activate SIRT 1 in order to inhibit OA disease progression. In the future, activating SIRT 1 via resveratrol with improved bioavailability may be an appropriate therapeutic approach for OA.
