Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China.
Department of Gastroenterology, The Gastroenterology Clinical Medical Center of Hainan Province, The Second Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China.
Curr Med Chem. 2024;31(42):7043-7058. doi: 10.2174/0109298673315146240731100101.
Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health.
CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines.
In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer.
The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration.
These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.
胃癌是最常见的胃肠道恶性肿瘤之一,对人类健康有重大负面影响。
CCL 趋化因子在多种肿瘤微环境中发挥重要作用;然而,胃癌与 CCL 趋化因子的关联却出人意料地有限。
在本研究中,我们综合利用了 cBioPortal、UALCAN、GEPIA、GeneMANIA、STRING 和 TRRUST 等生物信息学分析工具和数据库,以阐明 CCL 趋化因子在胃癌中的临床意义和生物学功能。
CCL1/3/4/5/7/8/14/15/18/20/21/22/26 的 mRNA 表达水平上调,而 CCL2/11/13/16/17/19/23/24/25/28 的 mRNA 表达水平下调。与胃癌病理分期显著相关的趋化因子是 CCL2/11/19/21。在胃癌中,CCL 趋化因子的表达水平与无病生存率无关,但 CCL14 的低表达与总生存率延长显著相关。其中,仅与 CCL 趋化因子的调节相关的转录因子有 10 个(RELA、NFKB1、STAT6、IRF3、REL、SPI1、STAT1、STAT3、JUN 和 SP1)。CCL 趋化因子的主要生物学过程和功能富集是诱导细胞定向迁移。
这些结果可能表明 CCL 趋化因子可能是胃癌的免疫治疗靶点和有前途的预后生物标志物。