肥大细胞线粒体活性相关基因可识别卵巢癌的不良预后和转移。
Mitochondrial activity related genes of mast cells identify poor prognosis and metastasis of ovarian cancer.
发表日期:2024 Jun 28
作者:
Xinghua Ma, Caryl Ligan, Shijia Huang, Yirong Chen, Muxin Li, Yuanyuan Cao, Wei Zhao, Shuli Zhao
来源:
Cellular & Molecular Immunology
摘要:
肿瘤浸润肥大细胞(TIM)在肿瘤中的促肿瘤或抗肿瘤作用不仅取决于癌症的类型和肿瘤进展的程度,还取决于它们在肿瘤体积中的位置。在我们的研究中,我们采用免疫组织化学方法揭示肿瘤基质中的肥大细胞(MC)与卵巢癌(OC)的转移呈正相关,但肿瘤实质中则不然。为了更深入地研究不同培养基质硬度对肿瘤实质和间质区域内 MC 生物学功能的影响,我们对二维 (2D) 或三维 (2D) 培养的小鼠 MC 系 (P815) 进行了转录组分析。 3D) 培养系统。进一步研究发现,较软的3D细胞外基质硬度可以提高MCs的线粒体活性,通过增加线粒体活性相关基因Pet100、atp5md和Cox7a2的表达水平来促进增殖。此外,采用LASSO回归分析,我们发现Pet100和Cox7a2与OC患者的预后密切相关。随后利用这两个基因构建了风险评分模型,揭示了高风险组模型是 OC 患者的预后因素之一。此外,XCell算法分析表明,高危人群表现出更广泛的免疫细胞浸润。我们的研究表明,肿瘤基质中的TIM可以促进OC的转移,线粒体活性相关蛋白Pet100/Cox7a2可以作为OC预后评估的生物标志物。版权所有©2024作者。由 Elsevier GmbH 出版。保留所有权利。
The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs' biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.