Zhang Ya, Chen Haoran, Zhang Wenzheng, Zhou Haiyan
Department of Pathology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Heliyon. 2024 Jul 2;10(13):e34005. doi: 10.1016/j.heliyon.2024.e34005. eCollection 2024 Jul 15.
Studies have indicated cancer-associated fibroblasts (CAFs) could have a significant impact in gastric cancer (GC) progression and chemotherapy resistance. However, the gene related to cancer fibroblasts that can be used as biomarkers to judge the occurrence of gastric cancer has not been fully explored. Based on two Gene Expression Omnibus (GEO) datasets, we focus on differentially expressed genes which may act as CAFs markers related to GC. Through COX regression, LASSO regression and Kaplan-Meier survival analysis, we discovered three upregulated genes (GLT8D2, GNAS and EDA) associated with poor GC patients' survival. By single-cell analysis and nomogram, we found that EDA may affect fibroblast production and disease prognosis in GC patients. EDA expression showed a positive correlation with 5-Fluorouracil IC50 values. Immunohistochemistry (IHC) and real time PCR indicated elevated EDA levels in GC tissues and cells. Enrichment analysis revealed that EDA was closely linked to immune system regulation. IHC and single-cell analysis indicated that EDA gene was associated with cancer fibroblasts marker FGF12 and influence cell interferon-gamma response, which may play a role in regulating immune-related characteristics. In summary, we concluded that EDA may be used as a new therapeutic CAFs marker for GC.
研究表明，癌症相关成纤维细胞（CAFs）可能对胃癌（GC）的进展和化疗耐药性产生重大影响。然而，与癌症成纤维细胞相关的、可作为判断胃癌发生的生物标志物的基因尚未得到充分探索。基于两个基因表达综合数据库（GEO）数据集，我们聚焦于可能作为与GC相关的CAFs标志物的差异表达基因。通过COX回归、LASSO回归和Kaplan-Meier生存分析，我们发现了三个与GC患者不良生存相关的上调基因（GLT8D2、GNAS和EDA）。通过单细胞分析和列线图，我们发现EDA可能影响GC患者的成纤维细胞生成和疾病预后。EDA表达与5-氟尿嘧啶IC50值呈正相关。免疫组织化学（IHC）和实时PCR表明GC组织和细胞中EDA水平升高。富集分析显示EDA与免疫系统调节密切相关。IHC和单细胞分析表明EDA基因与癌症成纤维细胞标志物FGF12相关，并影响细胞干扰素-γ反应，这可能在调节免疫相关特征中发挥作用。总之，我们得出结论，EDA可能用作GC的一种新的治疗性CAFs标志物。
