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TAF1D作为骨肉瘤中的一种新型生物标志物发挥作用。

TAF1D Functions as a Novel Biomarker in Osteosarcoma.

作者信息

Man Yu-Nan, Sun Yu, Chen Pei-Jun, Wu Hao, He Mao-Lin

机构信息

Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, Guangxi Zhuang Autonomous Region, P.R. China, 530021.

Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China. 530021 (Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China, 530021).

出版信息

J Cancer. 2023 Jul 9;14(11):2051-2065. doi: 10.7150/jca.85688. eCollection 2023.

Abstract

The most frequent primary bone cancer in teenagers, osteosarcoma (OS), is particularly aggressive with a high mortality rate. By combining public databases, OS and non-cancer samples were obtained. The Wilcoxon test and standardized mean difference (SMD) were utilized to evaluate the mRNA expression level of TATA-box binding protein associated factor, RNA polymerase 1 subunit D (TAF1D). The potential of TAF1D to discriminate OS samples from non-cancer samples was revealed by summary receiver operating characteristic curve (sROC). To investigate the prognostic significance, Kaplan‒Meier curve and univariate Cox analysis were performed. Immunohistochemistry (IHC) was used to determine the TAF1D protein expression level. ESTIMATE algorithm and TIMER2.0 database were used to reveal the association between TAF1D expression and the immune microenvironment. Enrichment analysis and potential drug prediction were performed to clarify the underlying molecular mechanisms and possible therapeutic directions of TAF1D. Ultimately, the transcription factors (TFs) and the TAF1D binding site were predicted based on the Cistrome and JASPAR databases. TAF1D was upregulated in OS at the mRNA and protein levels and possessed robust discriminatory power. TAF1D upregulation was suggestive of worse prognosis and enhancement of tumor purity in OS patients. The cell cycle was the most significantly enriched pathway, and NU.1025 was considered to be the potential target agent. Finally, MYC was identified as a TF that regulates the expression of TAF1D. Altogether, TAF1D has the potential to serve as a biological marker and therapeutic target in OS, which could offer new perspectives for OS treatment.

摘要

骨肉瘤(OS)是青少年中最常见的原发性骨癌,具有特别强的侵袭性和高死亡率。通过整合公共数据库,获取了骨肉瘤和非癌样本。采用Wilcoxon检验和标准化均值差(SMD)来评估TATA盒结合蛋白相关因子、RNA聚合酶1亚基D(TAF1D)的mRNA表达水平。通过汇总受试者工作特征曲线(sROC)揭示了TAF1D区分骨肉瘤样本和非癌样本的潜力。为了研究其预后意义,进行了Kaplan-Meier曲线分析和单因素Cox分析。采用免疫组织化学(IHC)检测TAF1D蛋白表达水平。利用ESTIMATE算法和TIMER2.0数据库揭示TAF1D表达与免疫微环境之间的关联。进行富集分析和潜在药物预测,以阐明TAF1D的潜在分子机制和可能的治疗方向。最终,基于Cistrome和JASPAR数据库预测了转录因子(TFs)和TAF1D结合位点。TAFISD在骨肉瘤中的mRNA和蛋白水平均上调,具有强大的鉴别能力。TAF1D上调提示骨肉瘤患者预后较差且肿瘤纯度增加。细胞周期是最显著富集的通路,NU.1025被认为是潜在的靶向药物。最后,鉴定出MYC是调节TAF1D表达的转录因子。总之,TAF1D有潜力作为骨肉瘤的生物标志物和治疗靶点,这可能为骨肉瘤治疗提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a21a/10367927/bfcfc9fd33dc/jcav14p2051g001.jpg

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