Zhang Ronghua, Liu Qiaofei, Peng Junya, Wang Mengyi, Li Tong, Liu Jingkai, Cui Ming, Zhang Xiang, Gao Xiang, Liao Quan, Zhao Yupei
Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
Department of Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.
J Cancer. 2020 Feb 10;11(9):2371-2381. doi: 10.7150/jca.40517. eCollection 2020.
: C-X-C motif chemokine 5 (CXCL5) is an important attractant for immune cell accumulation in tumor tissues. Recent evidence has shown that CXCL5 could promote carcinogenesis and cancer progression in a variety of cancer types. However, the relationships between CXCL5, immune cell infiltration and pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. This study aimed to explore the role and regulative mechanism of CXCL5 in PDAC carcinogenesis. : The expression of CXCL5 in PDAC was analyzed based on online databases and tissue microarray staining, and Western blotting of CXCL5 in PDAC cell lines and patient samples. The correlation between CXCL5 expression and clinicopathological features, prognosis and immune cell infiltration in tumor tissues was analyzed. : High expression of CXCL5 was observed both in PDAC tumor tissue and PDAC cell lines, compared to normal pancreas tissues and normal ductal epithelium cells. High CXCL5 expression in tumor tissues was positively correlated with an advanced T stage (p=0.036), a positive tumor lymph node metastasis (p=0.014), a poor differentiation status (p=0.003) and a poor prognosis (p=0.001). Combination of CA242 and CXCL5 expression (p<0.0001) served as a better prognostic factor than CA242 alone (p=0.006). In addition, PDAC patients with high CXCL5 expression had more intratumoral M2 polarized macrophages (p=0.0248), neutrophils (p=0.0068) and IgG plasma cells (p=0.0133) than patients with low CXCL5 expression. : The expression of CXCL5 is elevated in pancreatic cancer cells. High CXCL5 expression is positively correlated with poor survival and the increased infiltration of several types of immune suppressive cells. Thus, CXCL5 could be a promising therapeutic target for PDAC immunotherapy.
C-X-C基序趋化因子5(CXCL5)是肿瘤组织中免疫细胞聚集的重要吸引剂。最近的证据表明,CXCL5可促进多种癌症类型的致癌作用和癌症进展。然而,CXCL5、免疫细胞浸润与胰腺导管腺癌(PDAC)之间的关系仍 largely 未知。本研究旨在探讨CXCL5在PDAC致癌作用中的作用及调控机制。:基于在线数据库和组织芯片染色分析了CXCL5在PDAC中的表达,并对PDAC细胞系和患者样本进行了CXCL5的蛋白质印迹分析。分析了CXCL5表达与肿瘤组织临床病理特征、预后及免疫细胞浸润之间的相关性。:与正常胰腺组织和正常导管上皮细胞相比,在PDAC肿瘤组织和PDAC细胞系中均观察到CXCL5的高表达。肿瘤组织中CXCL5的高表达与T分期进展(p=0.036)、肿瘤淋巴结转移阳性(p=0.014)、低分化状态(p=0.003)和预后不良(p=0.001)呈正相关。CA242和CXCL5表达的联合(p<0.0001)比单独的CA242(p=0.006)是更好的预后因素。此外,与CXCL5低表达的患者相比,CXCL5高表达的PDAC患者肿瘤内M2极化巨噬细胞(p=0.0248)、中性粒细胞(p=0.0068)和IgG浆细胞(p=0.0133)更多。:CXCL5在胰腺癌细胞中的表达升高。CXCL5的高表达与不良生存及几种免疫抑制细胞浸润增加呈正相关。因此,CXCL5可能是PDAC免疫治疗的一个有前景的治疗靶点。