Sun Bai-Er, Yuan Zai-Xin, Wang Meng-Jiao, Xu Li-Qin, Feng Jian, Chen Jing-Jing
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, 20 Xi-Si Road, Nantong, 226001, Jiangsu, People's Republic of China.
Nantong University, Nantong, Jiangsu, China.
Discov Oncol. 2024 Jul 20;15(1):293. doi: 10.1007/s12672-024-01160-4.
Chemokine ligand 14, which has a C-C motif (CCL14), mediates the immunological milieu around tumors. However, its role in the progression of lung adenocarcinoma (LUAD) is still unknown. Our objectives were to study the association between CCL14 and tumor-infiltrating immune cells (TIICs) as well as the predictive significance of CCL14 in LUAD.
The expression of CCL14 in LUAD was examined by using the Oncomine, The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), and Human Protein Atlas databases. To determine the prognostic significance of CCL14 in LUAD, researchers used the Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA, version 2). We utilized TIMER and GEPIA2 to investigate the connection between CCL14 and TIICs. Gene set enrichment analysis (GSEA) was used to test for functional enrichment of genes. We used RT‒qPCR to measure CCL14 expression and Cell Counting Kit-8, Transwell, and wound healing assays to investigate the biological role of CCL14.
The prognosis of patients with LUAD was worse when CCL14 expression was low. Statistical analysis revealed that CCL14 mRNA expression was significantly greater in lung epithelial cells than in LUAD cell lines in vitro. Enhancing CCL14 expression reduced cell migration, invasion, and proliferation. The results of the immune infiltration research showed that CCL14 and TIICs were positively correlated. Different immune infiltration patterns associated with CCL14 were also shown by TIIC markers. According to GSEA, histone deacetylases, G2/M checkpoints, and Notch signaling pathways were associated with low CCL14 expression.
CCL14 is anticipated to emerge as a prognostic marker and therapeutic target for LUAD due to its role in regulating TIICs, suggesting that it may be an antioncogene.
具有C-C基序的趋化因子配体14（CCL14）介导肿瘤周围的免疫环境。然而，其在肺腺癌（LUAD）进展中的作用尚不清楚。我们的目的是研究CCL14与肿瘤浸润免疫细胞（TIICs）之间的关联以及CCL14在LUAD中的预测意义。
通过使用Oncomine、癌症基因组图谱（TCGA）、阿拉巴马大学伯明翰分校癌症数据分析门户（UALCAN）和人类蛋白质图谱数据库，检测LUAD中CCL14的表达。为了确定CCL14在LUAD中的预后意义，研究人员使用了Kaplan-Meier绘图仪和基因表达谱交互式分析（GEPIA，版本2）。我们利用TIMER和GEPIA2来研究CCL14与TIICs之间的联系。基因集富集分析（GSEA）用于测试基因的功能富集。我们使用逆转录定量聚合酶链反应（RT-qPCR）来测量CCL14的表达，并使用细胞计数试剂盒-8、Transwell和伤口愈合试验来研究CCL14的生物学作用。
CCL14表达低的LUAD患者预后较差。统计分析显示，体外肺上皮细胞中CCL14 mRNA表达明显高于LUAD细胞系。增强CCL14表达可减少细胞迁移、侵袭和增殖。免疫浸润研究结果表明，CCL14与TIICs呈正相关。TIIC标志物也显示了与CCL14相关的不同免疫浸润模式。根据GSEA，组蛋白脱乙酰酶、G2/M检查点和Notch信号通路与低CCL14表达相关。
由于CCL14在调节TIICs中的作用，预计它将成为LUAD的预后标志物和治疗靶点，表明它可能是一种抗癌基因。
