Anoikis-related PLCB4 is linked to immunotherapy response in osteosarcoma

Abstract

Osteosarcoma, the most common primary bone malignancy, poses significant management challenges due to its aggressiveness and metastatic potential. This study investigates the role of anoikis-related genes, particularly phospholipase C beta 4 (PLCB4), as a prognostic biomarker in osteosarcoma. We analyzed transcriptome data from the TARGET and GSE21257 cohorts using bioinformatics tools, identifying 15 significant genes, with PLCB4 as a key marker linked to decreased survival. Our findings indicate a negative correlation between PLCB4 and immune microenvironment scores and checkpoint molecules, suggesting its impact on immunotherapy responses. Drug sensitivity analyses revealed that high PLCB4 expression correlates with lower IC50 values for several chemotherapeutic agents. In vitro experiments showed that silencing PLCB4 inhibited cell proliferation and reduced PD-L1 expression. This study underscores the critical role of PLCB4 in osteosarcoma progression and its potential as a therapeutic target, offering insights into the molecular mechanisms of osteosarcoma biology and improving prognostic accuracy and treatment strategies.