He Chenglong, He Liping, Lu Qiaowei, Xiao Jianjun, Dong Wenjing
Department of Oncology, Zhongshan City People's Hospital Zhongshan 528400, Guangdong, China.
Guangdong Provincial People's Hospital Zhuhai Hospital Zhuhai 519040, Guangdong, China.
Am J Cancer Res. 2022 Jul 15;12(7):3034-3050. eCollection 2022.
Chemokine and chemokine receptors (CCRs) play a significant role in tumor infiltration of immune cells, tumor angiogenesis and distant metastasis. In this study, we explored the importance of CCRs in gastric cancer (GC) by analyzing the datasets from TCGA database. First, we analyzed the characteristics of the CCRs mutations. Then, we screened the differentially expressed CCRs and performed GO functional annotation and KEGG pathway analyses to explore their potential biological functions. Using multivariate Cox regression analyses, we constructed a prediction model based on four-CCRs (CCL15, CCL21, CCR3 and ACKR3) signature, and we found that the risk score of the model was an independent prognostic factor of GC. Next, a nomogram was constructed to assess the prognosis of GC patients. GSEA indicated that the high-risk group was significantly enriched in immune response and immune system process. Moreover, GSVA was employed to investigate the up- and down-regulated signaling pathways in the high- and low-risk groups. The correlation between risk score and immune-cell infiltration indicated that the four-CCRs signature might play a pivotal role in GC immune microenvironment. In conclusion, we revealed the potential molecular mechanisms of CCRs in GC and constructed a prediction model which might guide personalized treatment and prognosis for GC patients.
趋化因子和趋化因子受体(CCRs)在免疫细胞的肿瘤浸润、肿瘤血管生成和远处转移中发挥着重要作用。在本研究中,我们通过分析来自TCGA数据库的数据集,探讨了CCRs在胃癌(GC)中的重要性。首先,我们分析了CCRs突变的特征。然后,我们筛选了差异表达的CCRs,并进行了GO功能注释和KEGG通路分析,以探索它们潜在的生物学功能。使用多变量Cox回归分析,我们构建了一个基于四个CCRs(CCL15、CCL21、CCR3和ACKR3)特征的预测模型,并且我们发现该模型的风险评分是GC的一个独立预后因素。接下来,构建了一个列线图来评估GC患者的预后。GSEA表明,高风险组在免疫反应和免疫系统过程中显著富集。此外,采用GSVA来研究高风险组和低风险组中上调和下调的信号通路。风险评分与免疫细胞浸润之间的相关性表明,四个CCRs特征可能在GC免疫微环境中起关键作用。总之,我们揭示了CCRs在GC中的潜在分子机制,并构建了一个预测模型,该模型可能为GC患者的个性化治疗和预后提供指导。