Gu Xuyu, Zheng Shiya, Zhang Haifeng, Sun Xiaotong, Zhou Qin
School of Medicine, Southeast University, Nanjing, 210009, China.
Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Cancer Gene Ther. 2022 Dec;29(12):2001-2012. doi: 10.1038/s41417-022-00514-w. Epub 2022 Aug 10.
The association between cancer-associated fibroblasts (CAFs) and tumor microenvironment (TME) is a key factor in promoting tumor progression. However, the correlation between CAFs and TME in breast carcinoma has not been elucidated. Thus, further study about the cross-effect between CAFs and TME can provide novel strategies for breast carcinoma treatment, particularly targeted immunotherapy. First, we systematically analyzed cell communication in a single-cell dataset and identified the interacted genes between CAFs and TME components. Then, a robust fibroblast-related score (FRS) model was developed using the LASSO algorithm. The FRS can be a reliable adverse prognostic factor in three cohorts with breast carcinoma. Functional enrichment analysis and single-sample Gene Set Enrichment Analysis showed that patients with a high FRS had cold tumors with active proliferation and immunosuppression. Patients with a low FRS presented with hot tumors with active immune and cell-killing functions. Genomic variation analysis revealed that patients with a low FRS had a higher somatic mutation load and copy number variation burden. Finally, patients with a low FRS were more sensitive to chemotherapy and immunotherapy, particularly anti-PD-1 therapy. In conclusion, a reliable FRS model was constructed not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy and chemotherapy response for patients with BRCA, which might provide significant clinical implications for guiding clinical decision-making for patients with BRCA.
癌症相关成纤维细胞(CAFs)与肿瘤微环境(TME)之间的关联是促进肿瘤进展的关键因素。然而,乳腺癌中CAFs与TME之间的相关性尚未阐明。因此,进一步研究CAFs与TME之间的交叉效应可为乳腺癌治疗提供新策略,特别是靶向免疫治疗。首先,我们系统分析了单细胞数据集中的细胞通讯,并确定了CAFs与TME成分之间相互作用的基因。然后,使用LASSO算法开发了一个稳健的成纤维细胞相关评分(FRS)模型。FRS可能是三个乳腺癌队列中可靠的不良预后因素。功能富集分析和单样本基因集富集分析表明,FRS高的患者具有冷肿瘤,伴有活跃的增殖和免疫抑制。FRS低的患者表现为热肿瘤,具有活跃的免疫和细胞杀伤功能。基因组变异分析显示,FRS低的患者具有更高的体细胞突变负荷和拷贝数变异负担。最后,FRS低的患者对化疗和免疫治疗更敏感,尤其是抗PD-1治疗。总之,构建了一个可靠的FRS模型,不仅可用于预测预后,还能评估BRCA患者的临床免疫治疗和化疗反应,这可能为指导BRCA患者的临床决策提供重要的临床意义。