Bellah Sm Faysal, Sonia Fatema Akter, Ferdous Md Razowanul, Durojaye Olanrewaju Ayodeji, Islam Md Robiul
Department of Pharmacy, Manarat International University, Dhaka, Bangladesh.
Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science & Technology University, Gopalganj, Bangladesh.
Int J Breast Cancer. 2025 Jul 14;2025:8856457. doi: 10.1155/ijbc/8856457. eCollection 2025.
Breast cancer (BRCA) remains a leading cause of cancer-related mortality among women. CCL18 and EGF are implicated in tumor biology; however, their roles in BRCA remain partly defined. This study investigates their expression profiles, immune associations, prognostic relevance, epigenetic regulation, and molecular networks. Expression data from TCGA, UALCAN, and GSCA were analyzed to compare CCL18 and EGF levels in BRCA and normal tissues. Immune infiltration was assessed using TIMER, while survival analyses were performed via Kaplan-Meier plotter and TCGA subcohorts, including menopausal status. Promoter DNA methylation was examined using UALCAN. Gene correlation networks and protein-protein interactions were assessed using UALCAN and STRING. CCL18 was significantly upregulated in BRCA tissues, while EGF showed no consistent increase compared to normal tissue. Both genes were strongly correlated with immune cell infiltration. High CCL18 and EGF expression was associated with reduced relapse-free survival in BRCA. Promoter regions of both genes exhibited reduced DNA methylation, supporting their elevated expression in tumors. Interaction analyses revealed distinct immune- and signaling-related gene and protein networks. CCL18 shows strong prognostic and immunological relevance in BRCA, while EGF appears to play a broader oncogenic role. Hypomethylation of both genes may drive their aberrant expression and involvement in tumor progression.
乳腺癌(BRCA)仍然是女性癌症相关死亡的主要原因。CCL18和表皮生长因子(EGF)与肿瘤生物学有关;然而,它们在乳腺癌中的作用仍部分未明。本研究调查它们的表达谱、免疫关联、预后相关性、表观遗传调控及分子网络。分析来自癌症基因组图谱(TCGA)、UALCAN和基因集细胞分析(GSCA)的表达数据,以比较乳腺癌组织和正常组织中CCL18和EGF的水平。使用TIMER评估免疫浸润情况,同时通过Kaplan-Meier绘图仪和TCGA亚队列(包括绝经状态)进行生存分析。使用UALCAN检测启动子DNA甲基化。使用UALCAN和STRING评估基因相关网络和蛋白质-蛋白质相互作用。CCL18在乳腺癌组织中显著上调,而与正常组织相比,EGF未呈现一致的升高。这两个基因均与免疫细胞浸润密切相关。CCL18和EGF高表达与乳腺癌无复发生存期缩短有关。这两个基因的启动子区域均表现出DNA甲基化降低,支持它们在肿瘤中表达升高。相互作用分析揭示了不同的免疫和信号相关基因及蛋白质网络。CCL18在乳腺癌中显示出很强的预后和免疫学相关性,而EGF似乎发挥更广泛的致癌作用。这两个基因的低甲基化可能驱动它们的异常表达并参与肿瘤进展。