Comprehensive analysis reveals potential therapeutic targets and an integrated risk stratification model for solitary fibrous tumors
Ren-Jing Zhang, Yang Yang, Chunfang Hu, Mayan Huang, Wen‐Jian Cen, Dongyi Ling, Ya‐Kang Long, Xinhua Yang, Bo-Heng Xu, Junling Peng, Sujie Wang, Weijie Zhu, Mingbiao Wei, Jiaojiao Yang, Yuxia Xu, Xu Zhang, Jiangjun Ma, Fang Wang, Hong‐Tu Zhang, Peiqing Ma, Xiaojun Zhu, Guohui Song, Li‐Yue Sun, De‐Shen Wang, Feng‐Hua Wang, Yuhong Li, Sandro Santagata, Q. Li, Yan-Fen Feng, Ziming Du
Abstract
Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs.