AUTHOR=Liu Zhihui , Wu Jiasheng , Ji Hang , Zhao Hongtao , Wang Fang , Dong Jiawei , Zhang Jiheng , Wang Nan , Yan Xiuwei , Wang Kaikai , Hu Shaoshan
TITLE=Stromal protein CCN family contributes to the poor prognosis in lower-grade gioma by modulating immunity, matrix, stemness, and metabolism
JOURNAL=Frontiers in Molecular Biosciences
VOLUME=9
YEAR=2022
URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.1027236
DOI=10.3389/fmolb.2022.1027236
ISSN=2296-889X
ABSTRACT=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.