Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

Abstract

Abstract. C-X-C motif chemokine receptor type 2 (CXCR2), a key regulatory protein, has been associated with multiple roles in the progression of numerous tumors, including gastric adenocarcinoma (GA). However, the mechanism of CXCR2 in the development of tumors remains controversial and unclear. In a previous study, the expression of CXCR2 and interleukin-22 receptor 2 (IL-22BP) was observed in GA. This promoted the present study, which aimed to explore the association between the two proteins, and to further analyze their roles in GA. CXCR2 and IL-22BP protein expression was analyzed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in gastric cancer (GC) tissue, additionally confirmed via western blotting and immunocytochemical analysis in the MKN-45, BGC-823 and SGC-7901 cell lines. The association between expression levels and clinicopathological characteristics was evaluated by the Mann-Whitney U and Kruskal-Wallis tests. Using Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with non-cancerous tissue, CXCR2 and IL-22BP were over expressed (P<0.001 and P<0.001, respectively), and were observed mainly in the cytoplasm (P=0.022 and P=0.014, respectively) in GA. The associated protein and messenger RNA levels were analyzed, and coexpression was identified. Increased expression and more positive cases of CXCR2 and IL-22BP were observed with advanced pathological tumor-node-metastasis (p-TNM) stage in GC (P<0.001 and P<0.001, respectively), as well as the presence and absence of lymph node metastasis (LNM) (P=0.003 and P=0.041, respectively) and deep or superficial muscular invasion (P=0.002 and P=0.004, respectively). In addition, an association between IL-22BP and tumor diameter was indicated (P=0.021). In a Kaplan-Meier analysis, compared with negative expression, the two proteins identified a group of patients with the shortest OS. Cox proportional hazard models revealed that the two proteins, in addition to p-TNM stage, LNM and depth of invasion, predicted a short time to OS. The coexpression of CXCR2 and IL-22BP was demonstrated in GA, which may indicate that CXCR2 is involved in more complex mechanisms and roles, and indicate a poor outcome in GA progression.

The prognostic value of CXC chemokine receptor 2 (CXCR2) in cancers: a meta-analysis

“…Moreover, the criteria to distinguish the expression level of CXCR2 were different in the enrolled studies, which might impair the veracity of the prognosis value of CXCR2. In addition, although there was unfavorable prognostic value of CXCR2 in digestive tract cancer in previous 4 studies [ 15 – 18 ] while the other one by Liang et al [ 15 ] reported that CXCR2 indicates a better prognosis, in this meta-analysis, it was presented that no statistical significance was detected between high and low CXCR2 expression in subgroup analysis of digestive tract cancer in this meta-analysis. Hence, it was supposed that more clinical trials focused on the prognostic value of CXCR2 in digestive tract cancer should be conducted in the future.…”

“…The studies were conducted in 5 countries (9 Asian cohorts and 3 Caucasian cohorts), and they were published between 2012 and 2016. Studies concerning 5 digestive tract cancer (1 esophageal adenocarcinoma and squamous cell carcinoma procession cohort [ 15 ], 1 resected esophageal carcinoma cohort [ 16 ], 1 esophageal cancer cohort and 2 gastric cancer cohorts [ 17 , 18 ]) occupied the largest proportion of cancer type among all primary literatures, followed by lung cancer ( n = 2) [ 6 , 7 ], then laryngeal squamous cell carcinoma ( n = 1) [ 8 ], astrocytic tumors ( n = 1) [ 9 ], pancreatic ductal carcinoma ( n = 1) [ 10 ], clear-cell renal cell carcinoma ( n = 1) [ 11 ] and hepatocellular carcinoma ( n = 1) [ 12 ]. All studies reported the OS while only four studies reported the RFS.…”

Comparative transcriptomic analysis of porcine peripheral blood reveals differentially expressed genes from the cytokine–cytokine receptor interaction pathway related to health status

“…IL-22RA2 is associated with antimicrobial defense, protection against injury and regeneration (Huber et al 2012). Increased expression of IL-22RA2 was reported in gastric adenocarcinoma (Yang et al 2016) and inflammatory bowel disease (Pelczar et al 2016). Up-regulated transcriptional expression of IL-22RA2 was also documented in the case of hepatitis C virus infection (Sertorio et al 2015).…”

C-X-C motif chemokine receptor type 2 correlates with higher disease stages and predicts worse prognosis, and its downregulation enhances chemotherapy sensitivity in triple-negative breast cancer

“…CXCR2 is a G protein-coupled receptor that interacts with a wide range of chemokines, especially all angiogenic glutamic acid-leucine-arginine (ELR+) CXC chemokines that mediate angiogenic activity via interacting with CXCR2 (11,12,16). Recent studies have disclosed the role of CXCR2 in tumorigenesis and progression in vivo or in vitro (13,(17)(18)(19).…”