Wang Zhen, Fan Gentao, Zhu Hao, Yu Lingfeng, She Diankun, Wei Yanting, Huang Jianhao, Li Tianhang, Zhan Shoubin, Zhou Shenkai, Zhu Yan, Wang Yicun, Chen Xi, Zhao Jianning, Zhou Guangxin
Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Department of Orthopaedics, Affiliated Jianhu Hospital of Nantong University, Yancheng, China.
Front Oncol. 2022 Oct 5;12:980390. doi: 10.3389/fonc.2022.980390. eCollection 2022.
Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far.
The target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis . An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis . The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER.
PLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis and aggravated OS metastasis and angiogenesis . Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS.
PLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis and facilitated OS metastasis and angiogenesis . PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.
骨肉瘤(OS)是儿童和青少年中最常见的原发性恶性骨肿瘤。前胶原赖氨酸,2-氧戊二酸5-双加氧酶2(PLOD2)是介导稳定胶原交联形成的关键基因,在癌症进展中起重要作用。然而,迄今为止,骨肉瘤与PLOD2之间的相互作用尚未阐明。
通过我们自己的RNA测序结果以及来自基因表达综合数据库(GEO)的其他两个RNA测序结果筛选靶基因PLOD2。通过逆转录定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹法和免疫组织化学检测PLOD2在骨肉瘤中的表达。进行功能实验以研究PLOD2在骨肉瘤细胞侵袭、迁移和血管生成中的作用。建立骨肉瘤肺转移模型以研究PLOD2在骨肉瘤转移和血管生成中的功能。通过京都基因与基因组百科全书(KEGG)/基因本体论(GO)分析以及使用TARGET、癌症基因组图谱(TCGA)和肿瘤免疫评估资源(TIMER)的免疫浸润分析,探讨PLOD2在骨肉瘤免疫浸润中的作用。
PLOD2在骨肉瘤中高表达,这与骨肉瘤患者的不良预后相关。PLOD2促进骨肉瘤细胞迁移、侵袭和血管生成,并加重骨肉瘤转移和血管生成。生物信息学分析表明,PLOD2在骨肉瘤的免疫细胞浸润中起重要作用,包括CD8阳性T细胞、M0巨噬细胞、树突状细胞(DC细胞)、内皮细胞、未成熟DC细胞、ly内皮细胞、巨核细胞-红细胞祖细胞(MEP细胞)、mv内皮细胞、天然B细胞、平滑肌细胞和Th1细胞。免疫组织化学结果表明,在骨肉瘤中,CD4和CD8A的表达与PLOD2的表达呈负相关。
PLOD2在骨肉瘤中高表达,促进骨肉瘤迁移、侵袭和血管生成,并促进骨肉瘤转移和血管生成。PLOD2与骨肉瘤中的免疫细胞浸润相关,这可能是治疗骨肉瘤转移患者的一个有前景的靶点,并可在未来用于指导临床免疫治疗。