Li Xiaofang, Pan Zhiling, Luan Tiankuo, Xiao Qian, Li Liuying, Wu Qianxue, Yao Guoqing, Zhang Xiang, Song Daqiang
Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Department of Operating Room, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Front Immunol. 2024 Nov 29;15:1493673. doi: 10.3389/fimmu.2024.1493673. eCollection 2024.
Fibroblast Growth Factor Receptor (FGFR) signaling is linked with tumor progression and tumor immunoevasion, yet the potential effect of FGFR signature on the prognosis of patient with colorectal cancer (CRC) and response to immune therapy remains elusive.
The fibroblast growth factor receptor risk signature (FRS) was identified through single-cell RNA sequencing, bulk RNA sequencing, and machine learning techniques. Signaling enrichment analyses were conducted using Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Drugs targeting the FRS were predicted using the Cancer Therapeutics Response Portal (CTRP) and PRISM databases. The analysis of T cell function and the tumor microenvironment (TME) was performed using flow cytometry.
In this study, we characterized the FRS in cancer patients with CRC. By integrating advanced techniques, we identified the FRS and revealed the intricate molecular landscape and diversity of the FRS within the TME. Notably, the FRS effectively predicted unfavorable prognosis and resistance to immunotherapy in CRC patients. Furthermore, PHA-793887, identified as a potential FRS inhibitor by the CTRP and PRISM databases, significantly restructured the immunosuppressive TME and enhanced the antitumor immune response, resulting in a reduced tumor burden in the MC38 murine tumor model.
Together, these data support FRS positively correlates with poor prognosis and therapy resistance. The PHA-793887 could be a potential FRS inhibitor to improving the effectiveness of CRC management via bolstering antitumor immunity.
成纤维细胞生长因子受体（FGFR）信号传导与肿瘤进展和肿瘤免疫逃逸相关，但FGFR特征对结直肠癌（CRC）患者预后及免疫治疗反应的潜在影响仍不明确。
通过单细胞RNA测序、批量RNA测序和机器学习技术确定成纤维细胞生长因子受体风险特征（FRS）。使用基因集富集分析（GSEA）和京都基因与基因组百科全书（KEGG）进行信号富集分析。利用癌症治疗反应门户（CTRP）和PRISM数据库预测靶向FRS的药物。使用流式细胞术分析T细胞功能和肿瘤微环境（TME）。
在本研究中，我们对CRC癌症患者的FRS进行了特征描述。通过整合先进技术，我们确定了FRS，并揭示了TME内FRS复杂的分子格局和多样性。值得注意的是，FRS有效预测了CRC患者的不良预后和对免疫治疗的耐药性。此外，CTRP和PRISM数据库确定为潜在FRS抑制剂的PHA-793887显著重塑了免疫抑制性TME并增强了抗肿瘤免疫反应，导致MC38小鼠肿瘤模型中的肿瘤负担减轻。
总之，这些数据支持FRS与不良预后和治疗耐药性呈正相关。PHA-793887可能是一种潜在的FRS抑制剂，可通过增强抗肿瘤免疫力提高CRC治疗效果。
