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参与骨肉瘤的转移和生存过程。

involved in the metastasis and survival of osteosarcoma.

作者信息

Wan Rongxue, Yang Gu, Liu Qianzhen, Fu Xiaokang, Liu Zengping, Miao Huilai, Liu Huan, Huang Wenhua

机构信息

Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

出版信息

Front Oncol. 2022 Aug 22;12:965838. doi: 10.3389/fonc.2022.965838. eCollection 2022.

Abstract

Osteosarcoma is frequently metastasized at the time of diagnosis in patients. However, the underlying mechanism of osteosarcoma metastasis remains poorly understood. In this study, we evaluated DNA methylation profiles combined with gene expression profiles of 21 patients with metastatic osteosarcoma and 64 patients with non-metastatic osteosarcoma from TARGET database and identified and as hub genes related to the metastasis of osteosarcoma. To verify the effects of on migration and invasion of osteosarcoma, we performed wound-healing assay and transwell assay. The results showed that significantly inhibited the migration and invasion of osteosarcoma cells, and the Western blot experiments showed that the protein level of E-cad was upregulated and of VIM was downregulated in 143-B cell recombinant expression PKIB. These results indicate that PKIB inhibit the metastasis of osteosarcoma. CCK-8 assay results showed that PKIB promote the proliferation of osteosarcoma. In addition, the Western blot results showed that the phosphorylation level of Akt was upregulated in 143-B cells overexpressing PKIB, indicating that PKIB promotes the proliferation of osteosarcoma probably through signaling pathway that Akt involved in. These results give us clues that PKIB was a potential target for osteosarcoma therapy. Furthermore, combined clinical profiles analysis showed that the expression of - and - related risk scores was significantly related to the overall survival of patients with osteosarcoma. Thus, we constructed a nomogram based on and expression-related risk scores for osteosarcoma prognostic assessment to predict the 1-, 2-, 3-, and 5-year overall survival rate of patients with metastatic osteosarcoma, assisting clinicians in the diagnosis and treatment of metastatic osteosarcoma.

摘要

骨肉瘤患者在诊断时常常已经发生转移。然而,骨肉瘤转移的潜在机制仍知之甚少。在本研究中,我们从TARGET数据库评估了21例转移性骨肉瘤患者和64例非转移性骨肉瘤患者的DNA甲基化谱与基因表达谱,并鉴定出[具体基因1]和[具体基因2]作为与骨肉瘤转移相关的枢纽基因。为了验证[具体基因]对骨肉瘤迁移和侵袭的影响,我们进行了伤口愈合试验和Transwell试验。结果表明,[具体基因]显著抑制了骨肉瘤细胞的迁移和侵袭,蛋白质印迹实验表明,在143 - B细胞重组表达PKIB中,E - cad的蛋白水平上调而VIM的蛋白水平下调。这些结果表明PKIB抑制骨肉瘤的转移。CCK - 8试验结果表明PKIB促进骨肉瘤的增殖。此外,蛋白质印迹结果表明,在过表达PKIB的143 - B细胞中,Akt的磷酸化水平上调,表明PKIB可能通过Akt参与的信号通路促进骨肉瘤的增殖。这些结果为我们提供了线索,即PKIB是骨肉瘤治疗的潜在靶点。此外,联合临床特征分析表明,[具体基因1]和[具体基因2]相关风险评分的表达与骨肉瘤患者的总生存期显著相关。因此,我们基于[具体基因1]和[具体基因2]表达相关风险评分构建了列线图用于骨肉瘤预后评估,以预测转移性骨肉瘤患者1年、2年、3年和5年的总生存率,协助临床医生对转移性骨肉瘤进行诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf1/9441607/ff3f13838e5f/fonc-12-965838-g001.jpg

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