肥大细胞的线粒体活性相关基因可确定卵巢癌的不良预后和转移。

IF 2.5 4区 医学 Q3 IMMUNOLOGY Immunobiology Pub Date : 2024-06-28 DOI:10.1016/j.imbio.2024.152831
Xinghua Ma , Caryl Ligan , Shijia Huang , Yirong Chen , Muxin Li , Yuanyuan Cao , Wei Zhao , Shuli Zhao
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引用次数: 0

摘要

肿瘤浸润肥大细胞(TIMs)在肿瘤中的致癌或抗癌作用不仅取决于癌症类型和肿瘤进展程度,还取决于它们在肿瘤组织中的位置。在我们的研究中,我们采用免疫组化方法发现,肿瘤基质中的肥大细胞(MCs)与卵巢癌(OC)的转移呈正相关,但与肿瘤实质中的肥大细胞无关。为了深入研究不同培养基硬度对肿瘤实质和基质区域内肥大细胞生物学功能的影响,我们对在二维(2D)或三维(3D)培养系统中培养的小鼠 MC 株(P815)进行了转录组分析。进一步的研究发现,较软的三维细胞外基质硬度可以通过增加线粒体活性相关基因(即 Pet100、atp5md 和 Cox7a2)的表达水平来提高 MC 的线粒体活性,从而促进增殖。此外,通过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,我们利用这两个基因构建了一个风险评分模型,发现高风险组模型是 OC 患者的预后因素之一。此外,XCell 算法分析表明,高风险组的免疫细胞浸润范围更广。我们的研究发现,肿瘤基质中的TIMs可促进OC的转移,线粒体活性相关蛋白Pet100/Cox7a2可作为OC预后评估的生物标志物。
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Mitochondrial activity related genes of mast cells identify poor prognosis and metastasis of ovarian cancer

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.

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来源期刊
Immunobiology
Immunobiology 医学-免疫学
CiteScore
5.00
自引率
3.60%
发文量
108
审稿时长
55 days
期刊介绍: Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.
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