1. Multi-omics reveals the impact of cancer-associated fibroblasts on the prognosis and treatment response of adult diffuse highest-grade gliomas.
- Author
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Zhang G, Tai P, Fang J, Wang Z, Yu R, Yin Z, and Cao K
- Abstract
Background: Cancer associated fibroblasts (CAF), an important cancer-promoting and immunosuppressive component of the tumor immune microenvironment (TIME), have recently been found to infiltrate adult diffuse highest-grade gliomas (ADHGG) (gliomas of grade IV)., Methods: Gene expression and clinical data of ADHGG patients were obtained from the CGGA and TCGA databases. Consensus clustering was used to identify CAF subtypes based on CAF key genes acquired from single-cell omics and spatial transcriptomomics. CIBERSORT, ssGSEA, MCPcounter, and ESTIMATE analyses were used to assess the TIME of GBM. Survival analysis, drug sensitivity analysis, TCIA database, TIDE and cMap algorithms were used to compare the prognosis and treatment response between patients with different CAF subtypes. An artificial neural network (ANN) model based on random forest was constructed to exactly identify CAF subtypes, which was validated in a real-world patient cohort of ADHGG., Results: Consensus clustering classified ADHGG into two CAF subtypes. Compared with subtype B, patients with ADHGG subtype A had a poorer prognosis, worse responsiveness to immunotherapy and radiotherapy, higher CAF infiltration in TIME, but higher sensitivity to temozolomide. Furthermore, patients with subtype A had a much lower proportion of IDH mutations. Finally, the ANN model based on five genes (COL3A1, COL1A2, CD248, FN1, and COL1A1) could exactly discriminate CAF subtypes, and the validation of the real-world cohort indicated consistent results with the bioinformatics analyses., Conclusion: This study revealed a novel CAF subtype to distinguish ADHGG patients with different prognosis and treatment responsiveness, which may be helpful for accurate clinical decision-making of ADHGG., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ke Cao reports financial support was provided by the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China. Ke Cao reports financial support was provided by key research and development projects in Hunan Province. Ke Cao reports financial support was provided by Scientific research project of Hunan Provincial Health Commission. Ke Cao reports financial support was provided by the science and technology innovation Program of Hunan Province. Ke Cao reports financial support was provided by the Hunan Province Science and Technology Talent Promotion Project. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)
- Published
- 2024
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