Abstract:
Cholangiocarcinoma (CHOL) is a race malignant cancer arising from bile duct epithelial cells in clinical practice. C-X-C motif chemokine ligand 3 (CXCL3) is a member of chemokines family, which participates in the pathogenesis of various tumors. However, the association between CXCL3 and CHOL is unclear. This present study was to assess the role of CXCL3 expression in the progress of CHOL. TIMER, GEPIA, UALCAN, GSCA, LinkedOmics, Metascape and STRING databases were performed to evaluate the clinical and biological significances for CXCL3 with CHOL patients including expression, clinicopathological factors, immune cell infiltration, GO enrichment and KEGG pathway analyses, as well as PPI network analysis. The immunohistochemistry analysis of tissue microarray was conducted to detect the protein expression level, subcellular localization, clinicopathological factors and prognosis of CXCL3 in CHOL. The mRNA and protein expression levels of CXCL3 were markedly increased in CHOL tissues. The overexpression of CXCL3 was strongly associated with maximum tumor diameter of patients with CHOL. Additionally, there were negative correlations between the expression of CXCL3 and monocyte as well as Th17. Low infiltration of neutrophil indicated significantly shorter cumulative survival in CHOL patients. And CXCL3 was significantly associated with arm-level deletion of CD8+ T cell. Furthermore, functional network analysis suggested that CXCL3 and its associated genes were mainly enriched for chemotaxis, secretory granule membrane, cytokine activity and IL-17 signaling pathway. CXCL3 might potentially participate in the carcinogenesis of CHOL, which provided a direction for future research on the mechanism of CXCL3 in CHOL.
摘要:
胆管癌(CHOL)是临床实践中由胆管上皮细胞引起的种族恶性肿瘤。C-X-C基序趋化因子配体3(CXCL3)是趋化因子家族的一员,参与多种肿瘤的发病机制。然而,CXCL3和CHOL之间的关联尚不清楚.本研究旨在评估CXCL3表达在CHOL进展中的作用。TIMER,GEPIA,UALCAN,GSCA,LinkedOmics,Metascape和STRING数据库用于评估CXCL3与CHOL患者的临床和生物学意义,包括表达,临床病理因素,免疫细胞浸润,GO富集和KEGG途径分析,以及PPI网络分析。进行组织芯片的免疫组织化学分析以检测其蛋白表达水平,亚细胞定位,CHOL中CXCL3的临床病理因素和预后。CHOL组织中CXCL3的mRNA和蛋白表达水平明显升高。CXCL3的过度表达与CHOL患者的最大肿瘤直径密切相关。此外,CXCL3和Th17的表达与单核细胞呈负相关。中性粒细胞的低浸润表明CHOL患者的累积生存期明显较短。CXCL3与CD8+T细胞的臂水平缺失显著相关。此外,功能网络分析提示CXCL3及其相关基因主要富集趋化性,分泌颗粒膜,细胞因子活性和IL-17信号通路。CXCL3可能参与CHOL的癌变,为进一步研究CXCL3在CHOL中的作用机制提供了方向。