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与失巢凋亡相关的磷脂酶Cβ4与骨肉瘤的免疫治疗反应相关。

Anoikis-related PLCB4 is linked to immunotherapy response in osteosarcoma.

作者信息

Liu Guo, Fang Yu, Li Jiamiao, Chen Zhaofei

机构信息

Department of Spinal Surgery, Xianning Central Hospital, the First Affiliated Hospital of Hubei University of Science and Technology, Xianning, 437100, Hubei, China.

Department of Nephrology, Xianning Central Hospital, the First Affiliated Hospital of Hubei University of Science and Technology, Xianning, 437100, Hubei, China.

出版信息

Discov Oncol. 2025 Feb 22;16(1):226. doi: 10.1007/s12672-025-01970-0.

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.

摘要

骨肉瘤是最常见的原发性骨恶性肿瘤,因其侵袭性和转移潜能而带来重大的治疗挑战。本研究调查了失巢凋亡相关基因,特别是磷脂酶Cβ4(PLCB4)作为骨肉瘤预后生物标志物的作用。我们使用生物信息学工具分析了来自TARGET和GSE21257队列的转录组数据,确定了15个显著基因,其中PLCB4是与生存率降低相关的关键标志物。我们的研究结果表明,PLCB4与免疫微环境评分和检查点分子之间呈负相关,表明其对免疫治疗反应的影响。药物敏感性分析显示,PLCB4高表达与几种化疗药物的较低IC50值相关。体外实验表明,沉默PLCB4可抑制细胞增殖并降低PD-L1表达。本研究强调了PLCB4在骨肉瘤进展中的关键作用及其作为治疗靶点的潜力,为骨肉瘤生物学的分子机制提供了见解,并提高了预后准确性和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db1d/11846828/50f0a68f12cd/12672_2025_1970_Fig1_HTML.jpg

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