Huang Yanchun, Wu Lijuan, Sun Yong, Li Jiwen, Mao Nan, Yang Yeqing, Zhao Ming, Ren Sichong
Department of Laboratory Medicine, The First People's Hospital of Longquanyi District, Chengdu, Chengdu 610100, China.
Department of Laboratory Medicine, West China Longquan Hospital Sichuan University, Chengdu 610100, China.
Heliyon. 2023 Jul 13;9(7):e18215. doi: 10.1016/j.heliyon.2023.e18215. eCollection 2023 Jul.
Chemokine ligand 5 (CCL5), a vital member of the CC chemokine family, plays diverse roles in tumorigenesis, metastasis, and prognosis in various human tumors. However, no pan-cancer analysis has been conducted to illustrate its distinctive effects on clinical prognosis via underlying mechanisms and biological characteristics.
Herein, we exploited the existed public bioinformatics database, primarily TCGA database and GTEx data, to comprehensively analyze the value of CCL5 involved in patient prognosis.
This study found that CCL5 was excessively expressed in most tumors and significantly associated with clinical prognosis in 10 out of 33 types of tumors. Notably, CCL5 might be an independent predictive biomarker of clinical outcome in SKCM patients, confirmed by univariate and multivariate Cox regression analysis. Furthermore, we acquired the genetic alteration status of CCL5 in multiple types of tumor tissues from TCGA cohorts. We revealed a potential correlation between the expression level of CCL5 and tumor mutational burden in 33 types of tumors. In addition, data showed that DNA methylation was associated with CCL5 gene expression in THCA, PRAD, LUSC, and BRCA cancers. Immune infiltration and immune checkpoints are fine indexes for evaluating immunotherapy. We uncovered that CCL5 was negatively correlated with the immune infiltration of CD8 T cell, CD4 T cell, macrophages, and gamma delta T cells in BRCA-basal and CESC tumors, while a significant positive correlation was observed in BLCA, COAD and other 7 types of tumors. Besides, CCL5 was closely associated with the immune checkpoint molecules in 8 types of tumors. The TIDE score was less in the CCL5 high-expressed group than in the CCL5 low-expressed group in SKCM patients, which indicated that CCL5 might be a fine monitor of immune response for immunotherapy. GO enrichment analysis data uncovered that cytokine-cytokine receptor interaction and chemokine signaling might be involved in the role of CCL5 in regulating tumor pathogenesis and prognosis.
In conclusion, CCL5 was preliminarly identified as a biomarker of immune response and prognosis for tumors patients via our first comprehensive pan-cancer analysis.
趋化因子配体5（CCL5）是CC趋化因子家族的重要成员，在多种人类肿瘤的发生、转移和预后中发挥着多种作用。然而，尚未进行全癌分析来阐明其通过潜在机制和生物学特性对临床预后的独特影响。
在此，我们利用现有的公共生物信息学数据库，主要是TCGA数据库和GTEx数据，全面分析CCL5对患者预后的价值。
本研究发现CCL5在大多数肿瘤中过度表达，并且在33种肿瘤类型中的10种中与临床预后显著相关。值得注意的是，单因素和多因素Cox回归分析证实，CCL5可能是SKCM患者临床结局的独立预测生物标志物。此外，我们从TCGA队列中获得了多种肿瘤组织中CCL5的基因改变状态。我们揭示了33种肿瘤中CCL5表达水平与肿瘤突变负荷之间的潜在相关性。此外，数据显示DNA甲基化与THCA、PRAD、LUSC和BRCA癌症中的CCL5基因表达相关。免疫浸润和免疫检查点是评估免疫治疗的良好指标。我们发现，在BRCA-基底型和CESC肿瘤中，CCL5与CD8 T细胞、CD4 T细胞、巨噬细胞和γδ T细胞的免疫浸润呈负相关，而在BLCA、COAD和其他7种肿瘤中观察到显著正相关。此外，CCL5在8种肿瘤中与免疫检查点分子密切相关。SKCM患者中CCL5高表达组的TIDE评分低于CCL5低表达组，这表明CCL5可能是免疫治疗免疫反应的良好监测指标。GO富集分析数据揭示，细胞因子-细胞因子受体相互作用和趋化因子信号传导可能参与CCL5在调节肿瘤发病机制和预后中的作用。
总之，通过我们首次全面的全癌分析，CCL5初步被确定为肿瘤患者免疫反应和预后的生物标志物。
