Stromal protein CCN family contributes to the poor prognosis in lower-grade gioma by modulating immunity, matrix, stemness, and metabolism.
Stromal protein CCN family contributes to the poor prognosis in lower-grade gioma by modulating immunity, matrix, stemness, and metabolism.
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DOI：
10.3389/fmolb.2022.1027236
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
背景：基质蛋白CCN家族参与调控许多重要的生物学功能。然而，CCN蛋白失调在低级别胶质瘤（LGG）中的作用仍然知之甚少。方法：基于多个队列的RNA-seq图谱，探讨CCN蛋白的临床意义。采用LASSO回归分析构建CCNScore。利用PanCanAtlas数据和MEXPRESS数据库来阐明分子基础。结果：CCN4表达与LGG预后不良相关。CCNScore （CCN1 = 0.06, CCN4 = 0.86）对预后预测、亚型评估及治疗方案选择均有指导意义。高ccnscore组基因突变模式与胶质母细胞瘤相似，EGFR、PTEN、NF1多发突变。此外，高ccnscore组主要由经典样和间充质样样品组成，甲基化水平较低，干性较高，炎症程度较高，细胞外基质重塑水平较高，代谢途径功能障碍。另一方面，低ccnscore组主要由idh突变LGG组成，其特征是TP53、CIC和ATRX基因突变，高甲基化状态，低干性，低增殖，免疫安静和低细胞外基质刚度。结论：综上所述，这些结果概述了CCN家族在LGG中的作用，并提供了一个潜在的、有前景的治疗靶点。
Background: The CCN family of stromal proteins is involved in the regulation of many important biological functions. However, the role of dysregulated CCN proteins in lower-grade glioma (LGG) remain less understand. Methods: The clinical significance of the CCN proteins was explored based on RNA-seq profiles from multiple cohorts. A CCNScore was constructed using LASSO regression analysis. The PanCanAtlas data and MEXPRESS database were employed to elucidate molecular underpinnings. Results: The expression of CCN4 was associated with poor prognosis in LGG. The CCNScore (CCN1 = 0.06, CCN4 = 0.86) showed implication in prognosis prediction, subtype assessment and therapy selection. The gene mutation pattern of the high-CCNScore group was similar with glioblastoma, including EGFR, PTEN, and NF1 mutation frequently. Besides, the high-CCNScore group was comprised of samples mainly classic-like and mesenchymal-like, had lower methylation levels, higher stemness, higher inflammation, higher levels of extracellular matrix remodel and dysfunction of metabolic pathways. On the other hand, the low-CCNScore group consisted mainly of IDH-mutation LGG, and was characterized by TP53, CIC, and ATRX gene mutations, hyper-methylation status, lower stemness, lower proliferation, immune quietness and low extracellular matrix stiffness. Conclusion: In summary, these results outlined the role of CCN family in LGG and provided a potential and promising therapeutic target.
影响因子：
6.4
作者：
Yin, Dong;Chen, Weikai;O'Kelly, James;Lu, Daning;Ham, Michelle;Doan, Ngan B.;Xie, Dong;Wang, Charles;Vadgama, Jay;Said, Jonathan W.;Black, Keith L.;Koeffler, H. Phillip
通讯作者：
Koeffler, H. Phillip