Department of Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, China.
School of Rehabilitation Medicine, Shandong Second Medical University, Weifang, Shandong, China.
PeerJ. 2024 Feb 23;12:e16958. doi: 10.7717/peerj.16958. eCollection 2024.
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
为了阐明癌症相关成纤维细胞（CAFs）标志物与乳腺癌患者预后之间的关系，以便为个体化的 CAFs 靶向治疗提供依据。
检索从建库至 2023 年 9 月 PubMed、Web of Science、Cochrane、Embase 数据库中有关 CAFs 与乳腺癌患者的相关研究，采用 R 4.2.2 软件进行 Meta 分析，采用敏感性分析探索异质性来源，采用漏斗图和 Egger 检验评估发表偏倚。
共纳入 27 项研究，包含 6830 例患者。单因素分析显示，CAFs 中血小板衍生生长因子受体-（PDGFR-）（ =0.0055）、组织金属蛋白酶抑制剂-2（TIMP-2）（<0.0001）、基质金属蛋白酶（MMP）9（<0.0001）、MMP11（<0.0001）和 MMP13（=0.0009）高表达与复发无进展生存（RFS）/无病生存（DFS）/无转移生存（MFS）/无事件生存（EFS）降低相关。多因素分析显示，CAFs 中-平滑肌肌动蛋白（-SMA）（=0.0002）、足突蛋白（PDPN）（=0.0008）和 PDGFR-（=0.0470）高表达与 RFS/DFS/MFS/EFS 降低相关。此外，低分化乳腺癌患者 CAFs 中的 PDPN 和 PDGFR-表达高于相对分化较好的乳腺癌患者。此外，PDPN 表达与人类表皮生长因子受体-2（HER-2）呈正相关。
CAFs 中 -SMA、PDPN、PDGFR-高表达导致乳腺癌患者临床结局较差，提示其作为预后生物标志物和潜在治疗靶点的作用。
