Gao Yanqing, Bao Shuguang, Wen Bao, Li Haoyuan, Guo Qiang, Li Ao, Bao Luri, Li Meitao, Han Bateer
Department of Thoracic Tumor Surgery, Peking University Cancer Hospital (Inner Mongolia Campus) & Affiliated Cancer Hospital of Inner Mongolia Medical University, No. 42 Zhao Wu Da Road, Huhhot, Inner Mongolia Autonomous Region, 010020, China.
Inner Mongolia Medical University, No. 5 Xin Hua Road, Huhhot, Inner Mongolia Autonomous Region, 010050, China.
Funct Integr Genomics. 2025 Jul 11;25(1):154. doi: 10.1007/s10142-025-01660-8.
Cancer-associated fibroblasts (CAFs) serve as key stromal components within tumor microenvironment (TME), playing a significant role in the development and outcome of esophageal cancer (EC). There is an urgent need to identify genes related to CAFs to improve treatment strategies. The scRNA-sequencing dataset GSE196756 were used to identify fibroblast-related genes. Additionally, a WGCNA analysis was also conducted to identify modules related to CAFs within the TCGA-esophageal carcinoma (ESCA) cohort. By taking the intersection of identified genes of these two sections, CAF-related genes were identified. Expression of RGMA in EC samples compared to normal controls was assessed by RT-qPCR and western blot. In vitro and in vivo experiments were conducted to assess the impact of RGMA on EC cell growth. Compared to adjacent normal tissues, the levels of RGMA were notably reduced in EC tissues. Reduced RGMA levels were linked to a poor prognosis for EC patients. Furthermore, RGMA was found to have a positive correlation with the expression of fibroblast-related gene DCN, and showed a negative correlation with the expression of tumor-promoting chemokines, CXCL1, CXCL3 and CXCL8. Functionally, RGMA overexpression strongly prevented ECA109 cell viability, proliferation and migration, as well as suppresses tumor growth in vivo, suggesting that RGMA may function as a tumor suppressor in EC. Additionally, RGMA levels were also remarkably decreased in human esophageal CAFs relative to esophageal fibroblast cells (NFs). Importantly, the downregulation of RGMA may facilitate the transdifferentiation of NFs into CAFs by activating Akt signaling or upregulating CXCL1, CXCL3, and CXCL8, subsequently contributing to ECA109 cell proliferation. Collectively, RGMA may serve as a prognostic marker and a potential therapeutic target for EC. Clinical trial number Not applicable.
癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）中的关键基质成分，在食管癌（EC）的发展和预后中发挥着重要作用。迫切需要鉴定与CAFs相关的基因以改进治疗策略。使用单细胞核RNA测序数据集GSE196756来鉴定成纤维细胞相关基因。此外，还进行了加权基因共表达网络分析（WGCNA），以鉴定TCGA食管癌（ESCA）队列中与CAFs相关的模块。通过取这两部分鉴定出的基因的交集，确定了CAF相关基因。通过逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法评估EC样本中排斥导向分子A（RGMA）与正常对照相比的表达。进行体外和体内实验以评估RGMA对EC细胞生长的影响。与相邻正常组织相比，EC组织中RGMA水平显著降低。RGMA水平降低与EC患者的不良预后相关。此外，发现RGMA与成纤维细胞相关基因双调蛋白（DCN）的表达呈正相关，与促肿瘤趋化因子CXCL1、CXCL3和CXCL8的表达呈负相关。在功能上，RGMA过表达强烈抑制ECA109细胞活力、增殖和迁移，并在体内抑制肿瘤生长，表明RGMA可能在EC中起肿瘤抑制作用。此外，相对于食管成纤维细胞（NFs），人食管CAFs中的RGMA水平也显著降低。重要的是，RGMA的下调可能通过激活Akt信号或上调CXCL1、CXCL3和CXCL8促进NFs向CAFs的转分化，随后促进ECA109细胞增殖。总体而言，RGMA可能作为EC的预后标志物和潜在治疗靶点。临床试验编号：不适用。
