J Cancer 2020; 11(9):2371-2381. doi:10.7150/jca.40517 This issue

Research Paper

CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration

Ronghua Zhang1, Qiaofei Liu1, Junya Peng2, Mengyi Wang1, Tong Li1, Jingkai Liu1, Ming Cui1, Xiang Zhang1, Xiang Gao1, Quan Liao1✉, Yupei Zhao1✉

1. Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China
2. Department of Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China

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Citation:
Zhang R, Liu Q, Peng J, Wang M, Li T, Liu J, Cui M, Zhang X, Gao X, Liao Q, Zhao Y. CXCL5 overexpression predicts a poor prognosis in pancreatic ductal adenocarcinoma and is correlated with immune cell infiltration. J Cancer 2020; 11(9):2371-2381. doi:10.7150/jca.40517. Available from https://www.jcancer.org/v11p2371.htm

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Abstract

Background: 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.

Materials and Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: CXCL5, pancreatic ductal adenocarcinoma, prognosis, immune cell infiltration