HOXD9 是一种潜在的与胶质瘤免疫微环境相关的预后生物标志物。
HOXD9 is a potential prognostic biomarker involved in immune microenvironment of glioma.
机构信息
Phase I Clinical Trial Center, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
出版信息
J Cancer Res Clin Oncol. 2023 Nov;149(16):14911-14926. doi: 10.1007/s00432-023-05275-z. Epub 2023 Aug 21.
BACKGROUND
Glioma is the prevailing malignant tumor affecting the brain and central nervous system, constituting over 80% of all malignant brain tumors. HOXD9 has been implicated in the development of glioma, but the specific mechanism of its influence on glioma pathogenesis remains incompletely understood. The purpose of this study was to investigate the role of HOXD9 in glioma and examine the changes in HOXD9 expression during the progression of glioma, thus contributing new insights into the pathogenesis of glioma.
METHODS
Glioma samples from the Cancer Gene Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets were included in this study. Variations in HOXD9 expression in gliomas between different subgroups of multiple clinical characteristics were explored, and the expression was validated in glioma samples using qRT-PCR and western blotting. Next, the impact of HOXD9 on the prognosis of gliomas was explored by survival analysis, receiver operating characteristic curve, and nomogram plots. Subsequently, the association between HOXD9 and the tumor immune microenvironment was explored using the ssGSEA algorithm and the ESTIMATE algorithm. Then, immune-related pathways associated with HOXD9 were determined by differential express analysis and GSEA. Finally, HOXD9-related genomic alterations were identified.
RESULTS
HOXD9 expression is upregulated and correlated with malignant properties in glioma. Similarly, our validation results showed significantly upregulated protein and mRNA levels of HOXD9 in glioma brain tissues. In addition, high HOXD9 expression was indicative of a poor prognosis for glioma patients. Additionally, elevated HOXD9 levels were associated with reduced tumor purity and higher levels of immune invasion. Finally, HOXD9 was significantly associated with genomic alterations.
CONCLUSION
Overall, this study has unveiled a significant association between HOXD9 and the prognosis and survival of glioma patients. Our findings highlight the potential of HOXD9 as a prognostic biomarker, implicating its role in influencing the glioma immune microenvironment.
背景
脑胶质瘤是影响大脑和中枢神经系统的主要恶性肿瘤，占所有恶性脑肿瘤的 80%以上。HOXD9 参与了脑胶质瘤的发生，但它影响脑胶质瘤发病机制的具体机制尚不完全清楚。本研究旨在探讨 HOXD9 在脑胶质瘤中的作用，并研究 HOXD9 表达在脑胶质瘤进展过程中的变化，从而为脑胶质瘤的发病机制提供新的见解。
方法
本研究纳入了癌症基因图谱（TCGA）和中国脑胶质瘤基因组图谱（CGGA）数据集的脑胶质瘤样本。探讨了 HOXD9 在不同临床特征亚组的脑胶质瘤中的表达差异，并通过 qRT-PCR 和 Western blot 验证了脑胶质瘤样本中的表达。接着，通过生存分析、ROC 曲线和列线图探讨了 HOXD9 对脑胶质瘤预后的影响。随后，通过 ssGSEA 算法和 ESTIMATE 算法探讨了 HOXD9 与肿瘤免疫微环境的关系。接着，通过差异表达分析和 GSEA 确定与 HOXD9 相关的免疫相关通路。最后，鉴定与 HOXD9 相关的基因组改变。
结果
HOXD9 在脑胶质瘤中表达上调，并与恶性特征相关。同样，我们的验证结果显示 HOXD9 在脑胶质瘤组织中的蛋白和 mRNA 水平均显著上调。此外，HOXD9 高表达与脑胶质瘤患者预后不良相关。此外，HOXD9 水平升高与肿瘤纯度降低和免疫浸润水平升高有关。最后，HOXD9 与基因组改变显著相关。
结论
总的来说，本研究揭示了 HOXD9 与脑胶质瘤患者的预后和生存之间存在显著关联。我们的研究结果表明 HOXD9 作为一种潜在的预后生物标志物，可能影响脑胶质瘤的免疫微环境。
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